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Borrelia burgdorferi Complement Regulator-Aquiring Surface Protein 1

2013-09-12T20:24:49Z

Dipanshu Walia: Borrelia burgdorferi Complement Regulator-Aquiring Surface Protein 1 moved to Borrelia burgdorferi Complement Regulator-Acquiring Surface Protein 1: spelling change

#REDIRECT [[Borrelia burgdorferi Complement Regulator-Acquiring Surface Protein 1]]

Complement Regulator-Acquiring Surface Protein

2013-09-12T20:24:49Z

Dipanshu Walia: Borrelia burgdorferi Complement Regulator-Aquiring Surface Protein 1 moved to Borrelia burgdorferi Complement Regulator-Acquiring Surface Protein 1: spelling change

<Structure load='1w33' size='250' frame='true' align='right' caption='BbCRASP-1' scene='SB2013_L01gr6/Bbcrasp-1_no_spacefill/2' />

== '''Introduction''' ==

[http://en.wikipedia.org/wiki/Lyme_disease Lyme Disease] is caused by the [http://en.wikipedia.org/wiki/Spirochaete spirochete] [http://en.wikipedia.org/wiki/Borrelia_burgdorferi ''Borrelia burgdorferi''], and is transferred into vertebrate hosts by zoonotic vectors such as [http://en.wikipedia.org/wiki/Ixodes ''Ixodes''] ticks <ref name="Bykowski">PMID: 17562769</ref>. Lyme disease can result in multisystemic disorders, including cardiovascular and neurological problems. There are thousands of cases of Lyme disease reported each year, making it a prevalent disease in North America and Eurasia <ref name="Cordes">PMID: 15711564</ref>. In order for ''B. burgdorferi'' to survive in its host, it evades the host's immune system through the use of complement regulator-acquiring surface proteins. One such protein responsible for a successful initial infection is ''Borrelia burgdorferi'' complement regulator-acquiring surface protein 1, or BbCRASP-1 <ref name="Bykowski">PMID: 17562769</ref>. Because BbCRASP-1 binds host complement regulators to the spirochete's outer surface, ''B. burgdorferi'' remains undetected within the host <ref name="Bykowski">PMID: 17562769</ref>. BbCRASP-1 specifically binds to complement Factor H (FH) and Factor H-like proteins (FHL-1), which are responsible for the host's immune response and detection of pathogens <ref name="Kraiczy">PMID: 14607842</ref>. Recently, it was found that BbCRASP-1 binds to several other proteins in the extra cellular matrix of a human cell, making it highly flexible and adaptive.

<applet load='BBCRASP-12' size='250' frame='true' align='right' caption='BbCRASP-1' scene='Insert optional scene name here' />

== '''Structure''' ==

In nature, BbCRASP-1 exists as a homodimer bound to the spirochete's surface <ref name="Cordes">PMID: 15711564</ref>. BbCRASP-1 needs to be dimerized in order to bind FH/FHL-1 proteins. If its dimeric state is threatened, BbCRASP-1 would not be able to function.

=== '''Importance of the C-terminus''' ===

The C-terminus of BbCRASP-1 is a region crucial for its stability as a dimer. Previously,sequences of high conservation in the C-terminal regions of the protein’s monomers, <scene name='SB2013_L01gr6/C-terminus/1'>residues 241 to 250</scene> , were of interest as a potential binding site <ref name="Cordes">PMID: 15711564</ref>. Prior studies showed that deletion of these sites caused a complete inability of BbCRASP-1 to bind FH and FHL-1 regulators <ref name="Kraiczy">PMID: 14607842</ref>. The role of the C-terminus was determined by mutating <scene name='SB2013_L01gr6/Leucine_246/2'>leucine 246</scene> in this region of the dimer to aspartate <ref name="Cordes">PMID: 15711564</ref>. Both the C-terminally truncated and mutated BbCRASP-1 proteins lost their ability to dimerize, inhibiting them from binding to their host’s regulatory factors. It was then concluded that the C-terminus is a structurally sensitive region rather than a direct binding site <ref name="Cordes">PMID: 15711564</ref>. The C-terminus one monomer lies against the <scene name='SB2013_L01gr6/N-terminal_helix_ribbon/1'>N-terminal half of the E helix</scene> of the other and holds the <scene name='SB2013_L01gr6/Monomers_and_cterminus/1'>two monomers</scene> in place <ref name="Cordes">PMID: 15711564</ref>.

=== '''Other Potential Binding Sites''' ===

Additional studies were done to investigate the FH and FHL-1 binding sites on the protein. As with previous research, areas of high conservation were investigated due to their relationship with upholding the structure and function of the protein <ref name="CordesF">PMID: 16530476</ref>. Highly conserved areas of amino acid sequences among Borrelia CRASP-1 proteins encoded by the same gene were examined. The greatest homologous region was clustered on the <scene name='SB2013_L01gr6/Pocket_region_with_blue_fill/1'>center of the cleft region</scene> of the protein. A binding site in this region would be probable because this area allows more contact with the regulator proteins and would aid in further evasion of the immune system by shielding the binding domain from potential detection <ref name="CordesF">PMID: 16530476</ref>.

== '''Function''' ==

BbCRASP-1 can be found on the outer layer of the Lyme disease spirochete and is essential for the infiltration of the spirochete into the host <ref name="Bykowski">PMID: 17562769</ref>. BbCRASP-1 provides resistance for the spirochete against the host's complementary immune system as well as spreading of the spirochete within the host.

=== '''Host Immune Response Evasion''' ===

BbCRASP-1 has an affinity for [http://www.uniprot.org/uniprot/CFAH_HUMAN Factor H] (a regulatory protein secreted by the [http://en.wikipedia.org/wiki/Complement_system complement immune system]) and Factor H-like proteins. Therefore, Factor H binds to BbCRASP-1, which is bound to the outer surface of the spirochete. Because there are multiple BbCRASP-1 proteins on the spirochete, the spirochete is coated with Factor H and effectively able to infiltrate the host and go undetected in the host's plasma<ref name="Bykowski">PMID: 17562769</ref>.

=== '''Relation to the Extra Cellular Matrix''' ===

Recently it was found that BbCRASP-1 not only binds to FH and FHL-1 proteins, but it also binds to several other human ligands such as [http://www.uniprot.org/uniprot/BMP2_HUMAN BMP-2] and Extra cellular matrix ligands Collagen I, Collagen III, Collagen IV, fibronectin, laminin, and plasminogen <ref name"Hallstrom">PMID: 20565259</ref>. As a result of this new finding, BbCRASP-1 is said to not only advocate the bypassing of the complementary immune system, but facilitate the dissemination of ''B. burgdorferi'' within the host's tissues <ref name"Hallström">PMID: 20565259</ref>. Binding to the ECM of a host is common strategy used by pathogens to acquire contact within the host <ref name"Burgmann">PMID: 19118218</ref><ref name"Hallström">PMID: 16785539</ref>.

== '''Discussion''' ==

In order for ''B. burgdorferi'' to successfully colonize its new and hostile environment, it depends on a complement of proteins to fend off the host’s immune system. BbCRASP-1 is extremely important as it serves as a “frontier” protein, helping to bring upon successful initial infection to which depends the entire course of the pathogen’s life cycle and existence within the host. As such it remains a protein of high interest to medical researchers who can use this valuable information to stem the tide of the colonization process before it develops into a full case of Lyme disease. BbCRASP-1’s high affinity for FH and FHL-1 complement factors and other ligands such as BMP-2, Collagen I, Collagen III, Collagen
IV, fibronectin, laminin, and plasminogen make it a highly flexible and adaptive protein well suited to aiding the pathogen in colonization.

=== '''Future Studies''' ===

Further work needs to be done to determine the complement regulator protein and human ligand binding sites on BbCRASP-1. Knowing this information would aid in combating Lyme disease because it would give researchers a definite target for inhibitory drugs. However, with what is known about the protein, drugs that interfere with the C-terminus region of the dimer would also aid in mediating the effects of the disease because once the dimeric state of the protein is disrupted, it cannot function. These methods should also be applied to other CRASPs so FH/FHL-1 binding would be suppressed and the host's immune system can make a sizable defense against the invading spirochete.

== References ==

<references />

SB2013 L01gr6

2013-09-12T20:23:11Z

Dipanshu Walia: SB2013 L01gr6 moved to Borrelia burgdorferi Complement Regulator-Aquiring Surface Protein 1: It is a more appropriate title.

#REDIRECT [[Borrelia burgdorferi Complement Regulator-Aquiring Surface Protein 1]]

Complement Regulator-Acquiring Surface Protein

2013-09-12T20:23:11Z

Dipanshu Walia: SB2013 L01gr6 moved to Borrelia burgdorferi Complement Regulator-Aquiring Surface Protein 1: It is a more appropriate title.

Complement Regulator-Acquiring Surface Protein

2013-05-06T19:20:44Z

Dipanshu Walia:

Complement Regulator-Acquiring Surface Protein

2013-05-06T18:15:51Z

Dipanshu Walia:

<Structure load='1w33' size='250' frame='true' align='right' caption='BbCRASP-1' scene='SB2013_L01gr6/Bbcrasp-1_no_spacefill/2' />

== '''Introduction''' ==

[http://en.wikipedia.org/wiki/Lyme_disease Lyme Disease] is caused by the [http://en.wikipedia.org/wiki/Spirochaete spirochete] [http://en.wikipedia.org/wiki/Borrelia_burgdorferi ''Borrelia burgdorferi''], and is transferred into vertebrate hosts by zoonotic vectors such as [http://en.wikipedia.org/wiki/Ixodes ''Ixodes''] ticks <ref name="Bykowski">PMID: 17562769</ref>. Lyme disease can result in multisystemic disorders, including cardiovascular and neurological problems. There are thousands of cases of Lyme disease reported each year, making it a prevalent disease in North America and Eurasia <ref name="Cordes">PMID: 15711564</ref>. In order for ''B. burgdorferi'' to survive in its host, it evades the host's immune system through the use of complement regulator-acquiring surface proteins. One such protein responsible for a successful initial infection is ''Borrelia burgdorferi'' complement regulator-acquiring surface protein 1, or BbCRASP-1 <ref name="Bykowski">PMID: 17562769</ref>. Because BbCRASP-1 binds host complement regulators to the spirochete's outer surface, ''B. burgdorferi'' remains undetected within the host <ref name="Bykowski">PMID: 17562769</ref>. BbCRASP-1 specifically binds to complement Factor H (FH) and Factor H-like proteins (FHL-1), which are responsible for the host's immune response and detection of pathogens <ref name="Kraiczy">PMID: 14607842</ref>. Recently, it was found that BbCRASP-1 binds to several other proteins in the extra cellular matrix of a human cell, making it highly flexible and adaptive.

== '''Function''' ==

BbCRASP-1 can be found on the outer layer of the Lyme disease spirochete and is essential for the infiltration of the spirochete into the host <ref name="Bykowski">PMID: 17562769</ref>. BbCRASP-1 provides resistance for the spirochete against the host's complementary immune system as well as spreading of the spirochete within the host.

=== '''Host Immune Response Evasion''' ===

BbCRASP-1 has an affinity for [http://www.uniprot.org/uniprot/CFAH_HUMAN Factor H] (a regulatory protein secreted by the [http://en.wikipedia.org/wiki/Complement_system complement immune system]) and Factor H-like proteins. Therefore, Factor H binds to BbCRASP-1, which is bound to the outer surface of the spirochete. Because there are multiple BbCRASP-1 proteins on the spirochete, the spirochete is coated with Factor H and effectively able to infiltrate the host and go undetected in the host's plasma<ref name="Bykowski">PMID: 17562769</ref>.

=== '''Relation to the Extra Cellular Matrix''' ===

Recently it was found that BbCRASP-1 not only binds to FH and FHL-1 proteins, but it also binds to several other human ligands such as [http://www.uniprot.org/uniprot/BMP2_HUMAN BMP-2] and Extra cellular matrix ligands Collagen I, Collagen III, Collagen IV, fibronectin, laminin, and plasminogen <ref name"Hallstrom">PMID: 20565259</ref>. As a result of this new finding, BbCRASP-1 is said to not only advocate the bypassing of the complementary immune system, but facilitate the dissemination of ''B. burgdorferi'' within the host's tissues <ref name"Hallström">PMID: 20565259</ref>. Binding to the ECM of a host is common strategy used by pathogens to acquire contact within the host <ref name"Burgmann">PMID: 19118218</ref><ref name"Hallström">PMID: 16785539</ref>.

<applet load='BBCRASP-12' size='250' frame='true' align='right' caption='BbCRASP-1' scene='Insert optional scene name here' />

== '''Structure''' ==

In nature, BbCRASP-1 exists as a homodimer bound to the spirochete's surface <ref name="Cordes">PMID: 15711564</ref>. BbCRASP-1 needs to be dimerized in order to bind FH/FHL-1 proteins. If its dimeric state is threatened, BbCRASP-1 would not be able to function.

=== '''Importance of the C-terminus''' ===

The C-terminus of BbCRASP-1 is a region crucial for its stability as a dimer. Previously,sequences of high conservation in the C-terminal regions of the protein’s monomers, <scene name='SB2013_L01gr6/C-terminus/1'>residues 241 to 250</scene> , were of interest as a potential binding site <ref name="Cordes">PMID: 15711564</ref>. Prior studies showed that deletion of these sites caused a complete inability of BbCRASP-1 to bind FH and FHL-1 regulators <ref name="Kraiczy">PMID: 14607842</ref>. The role of the C-terminus was determined by mutating <scene name='SB2013_L01gr6/Leucine_246/2'>leucine 246</scene> in this region of the dimer to aspartate <ref name="Cordes">PMID: 15711564</ref>. Both the C-terminally truncated and mutated BbCRASP-1 proteins lost their ability to dimerize, inhibiting them from binding to their host’s regulatory factors. It was then concluded that the C-terminus is a structurally sensitive region rather than a direct binding site <ref name="Cordes">PMID: 15711564</ref>. The C-terminus one monomer lies against the <scene name='SB2013_L01gr6/N-terminal_helix_ribbon/1'>N-terminal half of the E helix</scene> of the other and holds the <scene name='SB2013_L01gr6/Monomers_and_cterminus/1'>two monomers</scene> in place <ref name="Cordes">PMID: 15711564</ref>.

=== '''Other Potential Binding Sites''' ===

Additional studies were done to investigate the FH and FHL-1 binding sites on the protein. As with previous research, areas of high conservation were investigated due to their relationship with upholding the structure and function of the protein <ref name="CordesF">PMID: 16530476</ref>. Highly conserved areas of amino acid sequences among Borrelia CRASP-1 proteins encoded by the same gene were examined. The greatest homologous region was clustered on the <scene name='SB2013_L01gr6/Pocket_region_with_blue_fill/1'>center of the cleft region</scene> of the protein. A binding site in this region would be probable because this area allows more contact with the regulator proteins and would aid in further evasion of the immune system by shielding the binding domain from potential detection <ref name="CordesF">PMID: 16530476</ref>.

== '''Discussion''' ==

In order for ''B. burgdorferi'' to successfully colonize its new and hostile environment, it depends on a complement of proteins to fend off the host’s immune system. BbCRASP-1 is extremely important as it serves as a “frontier” protein, helping to bring upon successful initial infection to which depends the entire course of the pathogen’s life cycle and existence within the host. As such it remains a protein of high interest to medical researchers who can use this valuable information to stem the tide of the colonization process before it develops into a full case of Lyme disease. BbCRASP-1’s high affinity for FH and FHL-1 complement factors and other ligands such as BMP-2, Collagen I, Collagen III, Collagen
IV, fibronectin, laminin, and plasminogen make it a highly flexible and adaptive protein well suited to aiding the pathogen in colonization.

=== '''Future Studies''' ===

Further work needs to be done to determine the complement regulator protein and human ligand binding sites on BbCRASP-1. Knowing this information would aid in combating Lyme disease because it would give researchers a definite target for inhibitory drugs. However, with what is known about the protein, drugs that interfere with the C-terminus region of the dimer would also aid in mediating the effects of the disease because once the dimeric state of the protein is disrupted, it cannot function. These methods should also be applied to other CRASPs so FH/FHL-1 binding would be suppressed and the host's immune system can make a sizable defense against the invading spirochete.

== References ==

<references />

Complement Regulator-Acquiring Surface Protein

2013-05-06T18:01:13Z

Dipanshu Walia:

<Structure load='1w33' size='250' frame='true' align='right' caption='BbCRASP-1' scene='Insert optional scene name here' />

== '''Introduction''' ==

[http://en.wikipedia.org/wiki/Lyme_disease Lyme Disease] is caused by the [http://en.wikipedia.org/wiki/Spirochaete spirochete] [http://en.wikipedia.org/wiki/Borrelia_burgdorferi ''Borrelia burgdorferi''], and is transferred into vertebrate hosts by zoonotic vectors such as [http://en.wikipedia.org/wiki/Ixodes ''Ixodes''] ticks <ref name="Bykowski">PMID: 17562769</ref>. Lyme disease can result in multisystemic disorders, including cardiovascular and neurological problems. There are thousands of cases of Lyme disease reported each year, making it a prevalent disease in North America and Eurasia <ref name="Cordes">PMID: 15711564</ref>. In order for ''B. burgdorferi'' to survive in its host, it evades the host's immune system through the use of complement regulator-acquiring surface proteins. One such protein responsible for a successful initial infection is ''Borrelia burgdorferi'' complement regulator-acquiring surface protein 1, or BbCRASP-1 <ref name="Bykowski">PMID: 17562769</ref>. Because BbCRASP-1 binds host complement regulators to the spirochete's outer surface, ''B. burgdorferi'' remains undetected within the host <ref name="Bykowski">PMID: 17562769</ref>. BbCRASP-1 specifically binds to complement Factor H (FH) and Factor H-like proteins (FHL-1), which are responsible for the host's immune response and detection of pathogens <ref name="Kraiczy">PMID: 14607842</ref>. Recently, it was found that BbCRASP-1 binds to several other proteins in the extra cellular matrix of a human cell, making it highly flexible and adaptive.

== '''Function''' ==

BbCRASP-1 can be found on the outer layer of the Lyme disease spirochete and is essential for the infiltration of the spirochete into the host <ref name="Bykowski">PMID: 17562769</ref>. BbCRASP-1 provides resistance for the spirochete against the host's complementary immune system as well as spreading of the spirochete within the host.

=== '''Host Immune Response Evasion''' ===

BbCRASP-1 has an affinity for [http://www.uniprot.org/uniprot/CFAH_HUMAN Factor H] (a regulatory protein secreted by the [http://en.wikipedia.org/wiki/Complement_system complement immune system]) and Factor H-like proteins. Therefore, Factor H binds to BbCRASP-1, which is bound to the outer surface of the spirochete. Because there are multiple BbCRASP-1 proteins on the spirochete, the spirochete is coated with Factor H and effectively able to infiltrate the host and go undetected in the host's plasma<ref name="Bykowski">PMID: 17562769</ref>.

=== '''Relation to the Extra Cellular Matrix''' ===

Recently it was found that BbCRASP-1 not only binds to FH and FHL-1 proteins, but it also binds to several other human ligands such as [http://www.uniprot.org/uniprot/BMP2_HUMAN BMP-2] and Extra cellular matrix ligands Collagen I, Collagen III, Collagen IV, fibronectin, laminin, and plasminogen <ref name"Hallstrom">PMID: 20565259</ref>. As a result of this new finding, BbCRASP-1 is said to not only advocate the bypassing of the complementary immune system, but facilitate the dissemination of ''B. burgdorferi'' within the host's tissues <ref name"Hallström">PMID: 20565259</ref>. Binding to the ECM of a host is common strategy used by pathogens to acquire contact within the host <ref name"Burgmann">PMID: 19118218</ref><ref name"Hallström">PMID: 16785539</ref>.

<applet load='BBCRASP-12' size='250' frame='true' align='right' caption='BbCRASP-1' scene='Insert optional scene name here' />

== '''Structure''' ==

In nature, BbCRASP-1 exists as a homodimer bound to the spirochete's surface <ref name="Cordes">PMID: 15711564</ref>. BbCRASP-1 needs to be dimerized in order to bind FH/FHL-1 proteins. If its dimeric state is threatened, BbCRASP-1 would not be able to function.

=== '''Importance of the C-terminus''' ===

The C-terminus of BbCRASP-1 is a region crucial for its stability as a dimer. Previously,sequences of high conservation in the C-terminal regions of the protein’s monomers, <scene name='SB2013_L01gr6/C-terminus/1'>residues 241 to 250</scene> , were of interest as a potential binding site <ref name="Cordes">PMID: 15711564</ref>. Prior studies showed that deletion of these sites caused a complete inability of BbCRASP-1 to bind FH and FHL-1 regulators <ref name="Kraiczy">PMID: 14607842</ref>. The role of the C-terminus was determined by mutating <scene name='SB2013_L01gr6/Leucine_246/2'>leucine 246</scene> in this region of the dimer to aspartate <ref name="Cordes">PMID: 15711564</ref>. Both the C-terminally truncated and mutated BbCRASP-1 proteins lost their ability to dimerize, inhibiting them from binding to their host’s regulatory factors. It was then concluded that the C-terminus is a structurally sensitive region rather than a direct binding site <ref name="Cordes">PMID: 15711564</ref>. The C-terminus one monomer lies against the <scene name='SB2013_L01gr6/N-terminal_helix_ribbon/1'>N-terminal half of the E helix</scene> of the other and holds the <scene name='SB2013_L01gr6/Monomers_and_cterminus/1'>two monomers</scene> in place <ref name="Cordes">PMID: 15711564</ref>.

=== '''Other Potential Binding Sites''' ===

Additional studies were done to investigate the FH and FHL-1 binding sites on the protein. As with previous research, areas of high conservation were investigated due to their relationship with upholding the structure and function of the protein <ref name="CordesF">PMID: 16530476</ref>. Highly conserved areas of amino acid sequences among Borrelia CRASP-1 proteins encoded by the same gene were examined. The greatest homologous region was clustered on the <scene name='SB2013_L01gr6/Pocket_region_with_blue_fill/1'>center of the cleft region</scene> of the protein. A binding site in this region would be probable because this area allows more contact with the regulator proteins and would aid in further evasion of the immune system by shielding the binding domain from potential detection <ref name="CordesF">PMID: 16530476</ref>.

== '''Discussion''' ==

In order for ''B. burgdorferi'' to successfully colonize its new and hostile environment, it depends on a complement of proteins to fend off the host’s immune system. BbCRASP-1 is extremely important as it serves as a “frontier” protein, helping to bring upon successful initial infection to which depends the entire course of the pathogen’s life cycle and existence within the host. As such it remains a protein of high interest to medical researchers who can use this valuable information to stem the tide of the colonization process before it develops into a full case of Lyme disease. BbCRASP-1’s high affinity for FH and FHL-1 complement factors and other ligands such as BMP-2, Collagen I, Collagen III, Collagen
IV, fibronectin, laminin, and plasminogen make it a highly flexible and adaptive protein well suited to aiding the pathogen in colonization.

=== '''Future Studies''' ===

Further work needs to be done to determine the complement regulator protein and human ligand binding sites on BbCRASP-1. Knowing this information would aid in combating Lyme disease because it would give researchers a definite target for inhibitory drugs. However, with what is known about the protein, drugs that interfere with the C-terminus region of the dimer would also aid in mediating the effects of the disease because once the dimeric state of the protein is disrupted, it cannot function. These methods should also be applied to other CRASPs so FH/FHL-1 binding would be suppressed and the host's immune system can make a sizable defense against the invading spirochete.

== References ==

<references />

Complement Regulator-Acquiring Surface Protein

2013-05-06T16:46:12Z

Dipanshu Walia:

<Structure load='1w33' size='250' frame='true' align='right' caption='BbCRASP-1' scene='Insert optional scene name here' />

== '''Introduction''' ==

[http://en.wikipedia.org/wiki/Lyme_disease Lyme Disease] is caused by the [http://en.wikipedia.org/wiki/Spirochaete spirochete] [http://en.wikipedia.org/wiki/Borrelia_burgdorferi ''Borrelia burgdorferi''], and is transferred into vertebrate hosts by zoonotic vectors such as [http://en.wikipedia.org/wiki/Ixodes ''Ixodes''] ticks <ref name="Bykowski">PMID: 17562769</ref>. Lyme disease can result in multisystemic disorders, including cardiovascular and neurological problems. There are thousands of cases of Lyme disease reported each year, making it a prevalent disease in North America and Eurasia <ref name="Cordes">PMID: 15711564</ref>. In order for ''B. burgdorferi'' to survive in its host, it evades the host's immune system through the use of complement regulator-acquiring surface proteins. One such protein responsible for a successful initial infection is ''Borrelia burgdorferi'' complement regulator-acquiring surface protein 1, or BbCRASP-1 <ref name="Bykowski">PMID: 17562769</ref>. Because BbCRASP-1 binds host complement regulators to the spirochete's outer surface, ''B. burgdorferi'' remains undetected within the host <ref name="Bykowski">PMID: 17562769</ref>. BbCRASP-1 specifically binds to complement Factor H (FH) and Factor H-like proteins (FHL-1), which are responsible for the host's immune response and detection of pathogens <ref name="Kraiczy">PMID: 14607842</ref>. Recently, it was found that BbCRASP-1 binds to several other proteins in the extra cellular matrix of a human cell, making it highly flexible and adaptive.

== '''Function''' ==

BbCRASP-1 can be found on the outer layer of the Lyme disease spirochete and is essential for the infiltration of the spirochete into the host <ref name="Bykowski">PMID: 17562769</ref>. BbCRASP-1 provides resistance for the spirochete against the host's complementary immune system as well as spreading of the spirochete within the host.

=== '''Host Immune Response Evasion''' ===

BbCRASP-1 has an affinity for [http://www.uniprot.org/uniprot/CFAH_HUMAN Factor H] (a regulatory protein secreted by the [http://en.wikipedia.org/wiki/Complement_system complement immune system]) and Factor H-like proteins. Therefore, Factor H binds to BbCRASP-1, which is bound to the outer surface of the spirochete. Because there are multiple BbCRASP-1 proteins on the spirochete, the spirochete is coated with Factor H and effectively able to infiltrate the host and go undetected in the host's plasma<ref name="Bykowski">PMID: 17562769</ref>.

=== '''Relation to the Extra Cellular Matrix''' ===

Recently it was found that BbCRASP-1 not only binds to FH and FHL-1 proteins, but it also binds to several other human ligands such as [http://www.uniprot.org/uniprot/BMP2_HUMAN BMP-2] and Extra cellular matrix ligands Collagen I, Collagen III, Collagen IV, fibronectin, laminin, and plasminogen <ref name"Hallstrom">PMID: 20565259</ref>. As a result of this new finding, BbCRASP-1 is said to not only advocate the bypassing of the complementary immune system, but facilitate the dissemination of ''B. burgdorferi'' within the host's tissues <ref name"Hallström">PMID: 20565259</ref>. Binding to the ECM of a host is common strategy used by pathogens to acquire contact within the host <ref name"Burgmann">PMID: 19118218</ref><ref name"Hallström">PMID: 16785539</ref>.

<applet load='BBCRASP-12' size='250' frame='true' align='right' caption='BbCRASP-1' scene='Insert optional scene name here' />

== '''Structure''' ==

In nature, BbCRASP-1 exists as a homodimer bound to the spirochete's surface <ref name="Cordes">PMID: 15711564</ref>. Researchers confirmed this by viewing the presence of pieces of the dimer in solution <ref name="Cordes">PMID: 15711564</ref>. They viewed the results through analytical ultracentrifugation and saw that dimeric crystals formed. If its dimeric state is threatened, BbCRASP-1 would not be able to function.

=== '''Importance of the C-terminus''' ===

Sequences of high conservation in the C-terminal regions of the protein’s monomers, <scene name='SB2013_L01gr6/C-terminus/1'>residues 241 to 250</scene> , were of interest as a potential binding site <ref name="Cordes">PMID: 15711564</ref>. Previous studies showed that deletion of these sites caused a complete inability of BbCRASP-1 to bind FH and FHL-1 regulators <ref name="Kraiczy">PMID: 14607842</ref>. The role of the C-terminus was determined by mutating <scene name='SB2013_L01gr6/Leucine_246/1'>leucine 246</scene> in this region of the dimer to aspartate <ref name="Cordes">PMID: 15711564</ref>. Both the C-terminally truncated and mutated BbCRASP-1 proteins lost their ability to dimerize, inhibiting them from binding to their host’s regulatory factors. It was then concluded that the C-terminus is a structurally sensitive region rather than a direct binding site <ref name="Cordes">PMID: 15711564</ref>. The C-terminus one monomer lies against the <scene name='SB2013_L01gr6/N-terminal_helix_ribbon/1'>N-terminal half of the E helix</scene> of the other and holds the <scene name='SB2013_L01gr6/Monomers_and_cterminus/1'>two monomers</scene> in place <ref name="Cordes">PMID: 15711564</ref>.

=== '''Other Potential Binding Sites''' ===

Additional studies were done to investigate the FH and FHL-1 binding sites on the protein. As with previous research, areas of high conservation were investigated due to their relationship with upholding the structure and function of the protein <ref name="CordesF">PMID: 16530476</ref>. Highly conserved areas of amino acid sequences among Borrelia CRASP-1 proteins encoded by the same gene were examined. The greatest homologous region was clustered on the <scene name='SB2013_L01gr6/Pocket_region_with_blue/1'>center of the cleft region</scene> of the protein. A binding site in this region would be probable because this area allows more contact with the regulator proteins and would aid in further evasion of the immune system by shielding the binding domain from potential detection <ref name="CordesF">PMID: 16530476</ref>.

== '''Discussion''' ==

In order for ''B. burgdorferi'' to successfully colonize its new and hostile environment, it depends on a complement of proteins to fend off the host’s immune system. BbCRASP-1 is extremely important as it serves as a “frontier” protein, helping to bring upon successful initial infection to which depends the entire course of the pathogen’s life cycle and existence within the host. As such it remains a protein of high interest to medical researchers who can use this valuable information to stem the tide of the colonization process before it develops into a full case of Lyme disease. BbCRASP-1’s high affinity for FH and FHL-1 complement factors and other ligands such as BMP-2, Collagen I, Collagen III, Collagen
IV, fibronectin, laminin, and plasminogen make it a highly flexible and adaptive protein well suited to aiding the pathogen in colonization.

=== '''Future Studies''' ===

Further work needs to be done to determine the complement regulator protein and human ligand binding sites on BbCRASP-1. Knowing this information would aid in combating Lyme disease because it would give researchers a definite target for inhibitory drugs. However, with what is known about the protein, drugs that interfere with the C-terminus region of the dimer would also aid in mediating the effects of the disease because once the dimeric state of the protein is disrupted, it cannot function. These methods should also be applied to other CRASPs so FH/FHL-1 binding would be suppressed and the host's immune system can make a sizable defense against the invading spirochete.

== References ==

<references />

Complement Regulator-Acquiring Surface Protein

2013-05-06T16:17:23Z

Dipanshu Walia:

<Structure load='1w33' size='250' frame='true' align='right' caption='BbCRASP-1' scene='Insert optional scene name here' />

== '''Introduction''' ==

Lyme disease is caused by the [http://en.wikipedia.org/wiki/Spirochaete spirochete] [http://en.wikipedia.org/wiki/Borrelia_burgdorferi ''Borrelia burgdorferi''], and is transferred into vertebrate hosts by zoonotic vectors such as [http://en.wikipedia.org/wiki/Ixodes ''Ixodes''] ticks <ref name="Bykowski">PMID: 17562769</ref>. There are thousands of cases of Lyme disease reported each year, making it a prevalent disease in North America and Eurasia <ref name="Cordes">PMID: 15711564</ref>. In order for ''B. burgdorferi'' to survive in its host, it evades the host's immune system through the use of complement regulator-acquiring surface proteins. One such protein responsible for a successful initial infection is ''Borrelia burgdorferi'' complement regulator-acquiring surface protein 1, or BbCRASP-1 <ref name="Bykowski">PMID: 17562769</ref>. Because BbCRASP-1 binds host complement regulators to the spirochete's outer surface, ''B. burgdorferi'' remains undetected within the host <ref name="Bykowski">PMID: 17562769</ref>. BbCRASP-1 specifically binds to complement Factor H (FH) and Factor H-like proteins (FHL-1), which are responsible for the host's immune response and detection of pathogens <ref name="Kraiczy">PMID: 14607842</ref>. Recently, it was found that BbCRASP-1 binds to several other proteins in the extra cellular matrix of a human cell, making it highly flexible and adaptive.

== '''Function''' ==

BbCRASP-1 can be found on the outer layer of the Lyme disease spirochete and is essential for the infiltration of the spirochete into the host <ref name="Bykowski">PMID: 17562769</ref>. BbCRASP-1 provides resistance for the spirochete against the host's complementary immune system as well as spreading of the spirochete within the host.

=== '''Host Immune Response Evasion''' ===

BbCRASP-1 has an affinity for [http://www.uniprot.org/uniprot/CFAH_HUMAN Factor H] (a regulatory protein secreted by the [http://en.wikipedia.org/wiki/Complement_system complement immune system]) and Factor H-like proteins. Therefore, Factor H binds to BbCRASP-1, which is bound to the outer surface of the spirochete. Because there are multiple BbCRASP-1 proteins on the spirochete, the spirochete is coated with Factor H and effectively able to infiltrate the host and go undetected in the host's plasma<ref name="Bykowski">PMID: 17562769</ref>.

=== '''Relation to the Extra Cellular Matrix''' ===

Recently it was found that BbCRASP-1 not only binds to FH and FHL-1 proteins, but it also binds to several other human ligands such as [http://www.uniprot.org/uniprot/BMP2_HUMAN BMP-2] and Extra cellular matrix ligands Collagen I, Collagen III, Collagen IV, fibronectin, laminin, and plasminogen <ref name"Hallstrom">PMID: 20565259</ref>. As a result of this new finding, BbCRASP-1 is said to not only advocate the bypassing of the complementary immune system, but facilitate the dissemination of ''B. burgdorferi'' within the host's tissues <ref name"Hallström">PMID: 20565259</ref>. Binding to the ECM of a host is common strategy used by pathogens to acquire contact within the host <ref name"Burgmann">PMID: 19118218</ref><ref name"Hallström">PMID: 16785539</ref>.

<applet load='BBCRASP-12' size='250' frame='true' align='right' caption='BbCRASP-1' scene='Insert optional scene name here' />

== '''Structure''' ==

In nature, BbCRASP-1 exists as a homodimer bound to the spirochete's surface <ref name="Cordes">PMID: 15711564</ref>. Researchers confirmed this by viewing the presence of pieces of the dimer in solution <ref name="Cordes">PMID: 15711564</ref>. They viewed the results through analytical ultracentrifugation and saw that dimeric crystals formed. If its dimeric state is threatened, BbCRASP-1 would not be able to function.

=== '''Importance of the C-terminus''' ===

Sequences of high conservation in the C-terminal regions of the protein’s monomers, <scene name='SB2013_L01gr6/C-terminus/1'>residues 241 to 250</scene> , were of interest as a potential binding site <ref name="Cordes">PMID: 15711564</ref>. Previous studies showed that deletion of these sites caused a complete inability of BbCRASP-1 to bind FH and FHL-1 regulators <ref name="Kraiczy">PMID: 14607842</ref>. The role of the C-terminus was determined by mutating <scene name='SB2013_L01gr6/Leucine_246/1'>leucine 246</scene> in this region of the dimer to aspartate <ref name="Cordes">PMID: 15711564</ref>. Both the C-terminally truncated and mutated BbCRASP-1 proteins lost their ability to dimerize, inhibiting them from binding to their host’s regulatory factors. It was then concluded that the C-terminus is a structurally sensitive region rather than a direct binding site <ref name="Cordes">PMID: 15711564</ref>. The C-terminus one monomer lies against the <scene name='SB2013_L01gr6/N-terminal_helix_ribbon/1'>N-terminal half of the E helix</scene> of the other and holds the <scene name='SB2013_L01gr6/Monomers_and_cterminus/1'>two monomers</scene> in place <ref name="Cordes">PMID: 15711564</ref>.

=== '''Other Potential Binding Sites''' ===

Additional studies were done to investigate the FH and FHL-1 binding sites on the protein. As with previous research, areas of high conservation were investigated due to their relationship with upholding the structure and function of the protein <ref name="CordesF">PMID: 16530476</ref>. Highly conserved areas of amino acid sequences among Borrelia CRASP-1 proteins encoded by the same gene were examined. The greatest homologous region was clustered on the <scene name='SB2013_L01gr6/Pocket_region_with_blue/1'>center of the cleft region</scene> of the protein. A binding site in this region would be probable because this area allows more contact with the regulator proteins and would aid in further evasion of the immune system by shielding the binding domain from potential detection <ref name="CordesF">PMID: 16530476</ref>.

== '''Discussion''' ==

In order for ''B. burgdorferi'' to successfully colonize its new and hostile environment, it depends on a complement of proteins to fend off the host’s immune system. BbCRASP-1 is extremely important as it serves as a “frontier” protein, helping to bring upon successful initial infection to which depends the entire course of the pathogen’s life cycle and existence within the host. As such it remains a protein of high interest to medical researchers who can use this valuable information to stem the tide of the colonization process before it develops into a full case of Lyme disease. BbCRASP-1’s high affinity for FH and FHL-1 complement factors and other ligands such as BMP-2, Collagen I, Collagen III, Collagen
IV, fibronectin, laminin, and plasminogen make it a highly flexible and adaptive protein well suited to aiding the pathogen in colonization.

=== '''Future Studies''' ===

Further work needs to be done to determine the complement regulator protein and human ligand binding sites on BbCRASP-1. Knowing this information would aid in combating Lyme disease because it would give researchers a definite target for inhibitory drugs. However, with what is known about the protein, drugs that interfere with the C-terminus region of the dimer would also aid in mediating the effects of the disease because once the dimeric state of the protein is disrupted, it cannot function. These methods should also be applied to other CRASPs so FH/FHL-1 binding would be suppressed and the host's immune system can make a sizable defense against the invading spirochete.

== References ==

<references />

Complement Regulator-Acquiring Surface Protein

2013-05-06T02:07:02Z

Dipanshu Walia: /* '''Host Immune Response Evasion''' */

<Structure load='1w33' size='250' frame='true' align='right' caption='BbCRASP-1' scene='Insert optional scene name here' />

== '''Introduction''' ==

Lyme disease is caused by the [http://en.wikipedia.org/wiki/Spirochaete spirochete] [http://en.wikipedia.org/wiki/Borrelia_burgdorferi ''Borrelia burgdorferi''], and is transferred into vertebrate hosts by zoonotic vectors such as ''Ixodes'' ticks <ref name="Bykowski">PMID: 17562769</ref>. There are thousands of cases of Lyme disease reported each year, making it a prevalent disease in North America and Eurasia <ref name="Cordes">PMID: 15711564</ref>. In order for ''B. burgdorferi'' to survive in its host, it evades the host's immune system through the use of complement regulator-acquiring surface proteins. One such protein responsible for a successful initial infection is ''Borrelia burgdorferi'' complement regulator-acquiring surface protein 1, or BbCRASP-1 <ref name="Bykowski">PMID: 17562769</ref>. Because BbCRASP-1 binds host complement regulators to the spirochete's outer surface, ''B. burgdorferi'' remains undetected within the host <ref name="Bykowski">PMID: 17562769</ref>. BbCRASP-1 specifically binds to complement Factor H (FH) and Factor H-like proteins (FHL-1), which are responsible for the host's immune response and detection of pathogens <ref name="Kraiczy">PMID: 14607842</ref>. Recently, it was found that BbCRASP-1 binds to several other proteins in the extra cellular matrix of a human cell.

== '''Function''' ==

BbCRASP-1 can be found on the outer layer of the Lyme disease spirochete and is essential for the infiltration of the spirochete into the host <ref name="Bykowski">PMID: 17562769</ref>. BbCRASP-1 provides resistance for the spirochete against the host's complementary immune system as well as spreading of the spirochete within the host.

=== '''Host Immune Response Evasion''' ===

BbCRASP-1 has an affinity for [http://www.uniprot.org/uniprot/CFAH_HUMAN Factor H] (a regulatory protein secreted by the [http://en.wikipedia.org/wiki/Complement_system complement immune system]) and Factor H-like proteins. Therefore, Factor H binds to BbCRASP-1, which is bound to the outer surface of the spirochete. Because there are multiple BbCRASP-1 proteins on the spirochete, the spirochete is coated with Factor H and effectively able to infiltrate the host and go undetected in the host's plasma<ref name="Bykowski">PMID: 17562769</ref>.

=== '''Relation to the Extra Cellular Matrix''' ===

Recently it was found that BbCRASP-1 not only binds to FH and FHL-1 proteins, but it also binds to several other human ligands such as [http://www.uniprot.org/uniprot/BMP2_HUMAN BMP-2] and Extra cellular matrix ligands Collagen I, Collagen III, Collagen IV, fibronectin, laminin, and plasminogen <ref name"Hallstrom">PMID: 20565259</ref>. As a result of this new finding, BbCRASP-1 is said to not only advocate the bypassing of the complementary immune system, but facilitate the dissemination of "B. burgdorferi" within the host's tissues <ref name"Hallström">PMID: 20565259</ref>. Binding to the ECM of a host is common strategy used by pathogens to acquire contact within the host <ref name"Burgmann">PMID: 19118218</ref><ref name"Hallström">PMID: 16785539</ref>.

<applet load='BBCRASP-12' size='250' frame='true' align='right' caption='BbCRASP-1' scene='Insert optional scene name here' />

== '''Structure''' ==

In nature, BbCRASP-1 exists as a homodimer bound to the spirochete's surface <ref name="Cordes">PMID: 15711564</ref>. Researchers confirmed this by viewing the presence of pieces of the dimer in solution <ref name="Cordes">PMID: 15711564</ref>. They viewed the results through analytical ultracentrifugation and saw that dimeric crystals formed. If its dimeric state is threatened, BbCRASP-1 would not be able to function.

=== '''Importance of the C-terminus''' ===

Sequences of high conservation in the C-terminal regions of the protein’s monomers, <scene name='SB2013_L01gr6/C-terminus/1'>residues 241 to 250</scene> , were of interest as a potential binding site <ref name="Cordes">PMID: 15711564</ref>. Previous studies showed that deletion of these sites caused a complete inability of BbCRASP-1 to bind FH and FHL-1 regulators <ref name="Kraiczy">PMID: 14607842</ref>. Scientists determined whether the role of the C-terminus region was in maintaining structure or directly functioning as a binding site by mutating <scene name='SB2013_L01gr6/Leucine_246/1'>leucine 246</scene> in the C-terminus region of the dimer to aspartate <ref name="Cordes">PMID: 15711564</ref>. Both the C-terminally truncated and mutated BbCRASP-1 proteins lost their ability to dimerize, inhibiting them from binding to their host’s regulatory factors. It was then concluded that the C-terminus is a structurally sensitive region rather than a direct binding site <ref name="Cordes">PMID: 15711564</ref>. The C-terminus one monomer lies against the <scene name='SB2013_L01gr6/N-terminal_helix/1'>N-terminal half of the helix</scene> of the other and holds the <scene name='SB2013_L01gr6/Monomers/1'>two monomers</scene> in place <ref name="Cordes">PMID: 15711564</ref>.

=== '''Other Potential Binding Sites''' ===

Additional studies were done to investigate the FH and FHL-1 binding sites on the protein. As with previous research, areas of high conservation were investigated due to their relationship with upholding the structure and function of the protein <ref name="CordesF">PMID: 16530476</ref>. Researchers examined highly conserved areas of amino acid sequences along the <scene name='SB2013_L01gr6/Pocket_region/3'>cleft region</scene> of the protein. They saw that the majority of these regions clustered on a highly-exposed region of the protein. A binding site in this region would be probable because this area allows more contact with the regulator proteins and would aid in further evasion of the immune system by shielding the binding domain from potential detection <ref name="CordesF">PMID: 16530476</ref>.

== References ==

<references />

Complement Regulator-Acquiring Surface Protein

2013-05-06T02:06:00Z

Dipanshu Walia:

<Structure load='1w33' size='250' frame='true' align='right' caption='BbCRASP-1' scene='Insert optional scene name here' />

== '''Introduction''' ==

Lyme disease is caused by the [http://en.wikipedia.org/wiki/Spirochaete spirochete] [http://en.wikipedia.org/wiki/Borrelia_burgdorferi ''Borrelia burgdorferi''], and is transferred into vertebrate hosts by zoonotic vectors such as ''Ixodes'' ticks <ref name="Bykowski">PMID: 17562769</ref>. There are thousands of cases of Lyme disease reported each year, making it a prevalent disease in North America and Eurasia <ref name="Cordes">PMID: 15711564</ref>. In order for ''B. burgdorferi'' to survive in its host, it evades the host's immune system through the use of complement regulator-acquiring surface proteins. One such protein responsible for a successful initial infection is ''Borrelia burgdorferi'' complement regulator-acquiring surface protein 1, or BbCRASP-1 <ref name="Bykowski">PMID: 17562769</ref>. Because BbCRASP-1 binds host complement regulators to the spirochete's outer surface, ''B. burgdorferi'' remains undetected within the host <ref name="Bykowski">PMID: 17562769</ref>. BbCRASP-1 specifically binds to complement Factor H (FH) and Factor H-like proteins (FHL-1), which are responsible for the host's immune response and detection of pathogens <ref name="Kraiczy">PMID: 14607842</ref>. Recently, it was found that BbCRASP-1 binds to several other proteins in the extra cellular matrix of a human cell.

== '''Function''' ==

BbCRASP-1 can be found on the outer layer of the Lyme disease spirochete and is essential for the infiltration of the spirochete into the host <ref name="Bykowski">PMID: 17562769</ref>. BbCRASP-1 provides resistance for the spirochete against the host's complementary immune system as well as spreading of the spirochete within the host.

=== '''Host Immune Response Evasion''' ===

BbCRASP-1 has an affinity for [http://www.uniprot.org/uniprot/CFAH_HUMAN Factor H] (a regulatory protein secreted by the [http://en.wikipedia.org/wiki/Complement_system complement immune system) and Factor H-like proteins. Therefore, Factor H binds to BbCRASP-1, which is bound to the outer surface of the spirochete. Because there are multiple BbCRASP-1 proteins on the spirochete, the spirochete is coated with Factor H and effectively able to infiltrate the host and go undetected in the host's plasma<ref name="Bykowski">PMID: 17562769</ref>.

=== '''Relation to the Extra Cellular Matrix''' ===

Recently it was found that BbCRASP-1 not only binds to FH and FHL-1 proteins, but it also binds to several other human ligands such as [http://www.uniprot.org/uniprot/BMP2_HUMAN BMP-2] and Extra cellular matrix ligands Collagen I, Collagen III, Collagen IV, fibronectin, laminin, and plasminogen <ref name"Hallstrom">PMID: 20565259</ref>. As a result of this new finding, BbCRASP-1 is said to not only advocate the bypassing of the complementary immune system, but facilitate the dissemination of "B. burgdorferi" within the host's tissues <ref name"Hallström">PMID: 20565259</ref>. Binding to the ECM of a host is common strategy used by pathogens to acquire contact within the host <ref name"Burgmann">PMID: 19118218</ref><ref name"Hallström">PMID: 16785539</ref>.

<applet load='BBCRASP-12' size='250' frame='true' align='right' caption='BbCRASP-1' scene='Insert optional scene name here' />

== '''Structure''' ==

In nature, BbCRASP-1 exists as a homodimer bound to the spirochete's surface <ref name="Cordes">PMID: 15711564</ref>. Researchers confirmed this by viewing the presence of pieces of the dimer in solution <ref name="Cordes">PMID: 15711564</ref>. They viewed the results through analytical ultracentrifugation and saw that dimeric crystals formed. If its dimeric state is threatened, BbCRASP-1 would not be able to function.

=== '''Importance of the C-terminus''' ===

Sequences of high conservation in the C-terminal regions of the protein’s monomers, <scene name='SB2013_L01gr6/C-terminus/1'>residues 241 to 250</scene> , were of interest as a potential binding site <ref name="Cordes">PMID: 15711564</ref>. Previous studies showed that deletion of these sites caused a complete inability of BbCRASP-1 to bind FH and FHL-1 regulators <ref name="Kraiczy">PMID: 14607842</ref>. Scientists determined whether the role of the C-terminus region was in maintaining structure or directly functioning as a binding site by mutating <scene name='SB2013_L01gr6/Leucine_246/1'>leucine 246</scene> in the C-terminus region of the dimer to aspartate <ref name="Cordes">PMID: 15711564</ref>. Both the C-terminally truncated and mutated BbCRASP-1 proteins lost their ability to dimerize, inhibiting them from binding to their host’s regulatory factors. It was then concluded that the C-terminus is a structurally sensitive region rather than a direct binding site <ref name="Cordes">PMID: 15711564</ref>. The C-terminus one monomer lies against the <scene name='SB2013_L01gr6/N-terminal_helix/1'>N-terminal half of the helix</scene> of the other and holds the <scene name='SB2013_L01gr6/Monomers/1'>two monomers</scene> in place <ref name="Cordes">PMID: 15711564</ref>.

=== '''Other Potential Binding Sites''' ===

Additional studies were done to investigate the FH and FHL-1 binding sites on the protein. As with previous research, areas of high conservation were investigated due to their relationship with upholding the structure and function of the protein <ref name="CordesF">PMID: 16530476</ref>. Researchers examined highly conserved areas of amino acid sequences along the <scene name='SB2013_L01gr6/Pocket_region/3'>cleft region</scene> of the protein. They saw that the majority of these regions clustered on a highly-exposed region of the protein. A binding site in this region would be probable because this area allows more contact with the regulator proteins and would aid in further evasion of the immune system by shielding the binding domain from potential detection <ref name="CordesF">PMID: 16530476</ref>.

== References ==

<references />

Complement Regulator-Acquiring Surface Protein

2013-05-06T02:02:58Z

Dipanshu Walia: /* '''Host Immune Response Evasion''' */

<Structure load='1w33' size='250' frame='true' align='right' caption='BbCRASP-1' scene='Insert optional scene name here' />

== '''Introduction''' ==

Lyme disease is caused by the [http://en.wikipedia.org/wiki/Spirochaete spirochete] [http://en.wikipedia.org/wiki/Borrelia_burgdorferi ''Borrelia burgdorferi''], and is transferred into vertebrate hosts by zoonotic vectors such as ''Ixodes'' ticks <ref name="Bykowski">PMID: 17562769</ref>. There are thousands of cases of Lyme disease reported each year, making it a prevalent disease in North America and Eurasia <ref name="Cordes">PMID: 15711564</ref>. In order for ''B. burgdorferi'' to survive in its host, it evades the host's immune system through the use of complement regulator-acquiring surface proteins. One such protein responsible for a successful initial infection is ''Borrelia burgdorferi'' complement regulator-acquiring surface protein 1, or BbCRASP-1 <ref name="Bykowski">PMID: 17562769</ref>. Because BbCRASP-1 binds host complement regulators to the spirochete's outer surface, ''B. burgdorferi'' remains undetected within the host <ref name="Bykowski">PMID: 17562769</ref>. BbCRASP-1 specifically binds to complement Factor H (FH) and Factor H-like proteins (FHL-1), which are responsible for the host's immune response and detection of pathogens <ref name="Kraiczy">PMID: 14607842</ref>. Recently, it was found that BbCRASP-1 binds to several other proteins in the extra cellular matrix of a human cell.

== '''Function''' ==

BbCRASP-1 can be found on the outer layer of the Lyme disease spirochete and is essential for the infiltration of the spirochete into the host <ref name="Bykowski">PMID: 17562769</ref>. BbCRASP-1 provides resistance for the spirochete against the host's complementary immune system as well as spreading of the spirochete within the host.

=== '''Host Immune Response Evasion''' ===

BbCRASP-1 has an affinity for Factor H (a regulatory protein secreted by the complement immune system) and Factor H-like proteins. Therefore, Factor H binds to BbCRASP-1, which is bound to the outer surface of the spirochete. Because there are multiple BbCRASP-1 proteins on the spirochete, the spirochete is coated with [http://www.uniprot.org/uniprot/CFAH_HUMAN Factor H] and effectively able to infiltrate the host and go undetected in the host's plasma<ref name="Bykowski">PMID: 17562769</ref>.

=== '''Relation to the Extra Cellular Matrix''' ===

Recently it was found that BbCRASP-1 not only binds to FH and FHL-1 proteins, but it also binds to several other human ligands such as [http://www.uniprot.org/uniprot/BMP2_HUMAN BMP-2] and Extra cellular matrix ligands Collagen I, Collagen III, Collagen IV, fibronectin, laminin, and plasminogen <ref name"Hallstrom">PMID: 20565259</ref>. As a result of this new finding, BbCRASP-1 is said to not only advocate the bypassing of the complementary immune system, but facilitate the dissemination of "B. burgdorferi" within the host's tissues <ref name"Hallström">PMID: 20565259</ref>. Binding to the ECM of a host is common strategy used by pathogens to acquire contact within the host <ref name"Burgmann">PMID: 19118218</ref><ref name"Hallström">PMID: 16785539</ref>.

<applet load='BBCRASP-12' size='250' frame='true' align='right' caption='BbCRASP-1' scene='Insert optional scene name here' />

== '''Structure''' ==

In nature, BbCRASP-1 exists as a homodimer bound to the spirochete's surface <ref name="Cordes">PMID: 15711564</ref>. Researchers confirmed this by viewing the presence of pieces of the dimer in solution <ref name="Cordes">PMID: 15711564</ref>. They viewed the results through analytical ultracentrifugation and saw that dimeric crystals formed. If its dimeric state is threatened, BbCRASP-1 would not be able to function.

=== '''Importance of the C-terminus''' ===

Sequences of high conservation in the C-terminal regions of the protein’s monomers, <scene name='SB2013_L01gr6/C-terminus/1'>residues 241 to 250</scene> , were of interest as a potential binding site <ref name="Cordes">PMID: 15711564</ref>. Previous studies showed that deletion of these sites caused a complete inability of BbCRASP-1 to bind FH and FHL-1 regulators <ref name="Kraiczy">PMID: 14607842</ref>. Scientists determined whether the role of the C-terminus region was in maintaining structure or directly functioning as a binding site by mutating <scene name='SB2013_L01gr6/Leucine_246/1'>leucine 246</scene> in the C-terminus region of the dimer to aspartate <ref name="Cordes">PMID: 15711564</ref>. Both the C-terminally truncated and mutated BbCRASP-1 proteins lost their ability to dimerize, inhibiting them from binding to their host’s regulatory factors. It was then concluded that the C-terminus is a structurally sensitive region rather than a direct binding site <ref name="Cordes">PMID: 15711564</ref>. The C-terminus one monomer lies against the <scene name='SB2013_L01gr6/N-terminal_helix/1'>N-terminal half of the helix</scene> of the other and holds the <scene name='SB2013_L01gr6/Monomers/1'>two monomers</scene> in place <ref name="Cordes">PMID: 15711564</ref>.

=== '''Other Potential Binding Sites''' ===

Additional studies were done to investigate the FH and FHL-1 binding sites on the protein. As with previous research, areas of high conservation were investigated due to their relationship with upholding the structure and function of the protein <ref name="CordesF">PMID: 16530476</ref>. Researchers examined highly conserved areas of amino acid sequences along the <scene name='SB2013_L01gr6/Pocket_region/3'>cleft region</scene> of the protein. They saw that the majority of these regions clustered on a highly-exposed region of the protein. A binding site in this region would be probable because this area allows more contact with the regulator proteins and would aid in further evasion of the immune system by shielding the binding domain from potential detection <ref name="CordesF">PMID: 16530476</ref>.

== References ==

<references />

Complement Regulator-Acquiring Surface Protein

2013-05-06T01:55:53Z

Dipanshu Walia:

<Structure load='1w33' size='250' frame='true' align='right' caption='BbCRASP-1' scene='Insert optional scene name here' />

== '''Introduction''' ==

Lyme disease is caused by the [http://en.wikipedia.org/wiki/Spirochaete spirochete] [http://en.wikipedia.org/wiki/Borrelia_burgdorferi ''Borrelia burgdorferi''], and is transferred into vertebrate hosts by zoonotic vectors such as ''Ixodes'' ticks <ref name="Bykowski">PMID: 17562769</ref>. There are thousands of cases of Lyme disease reported each year, making it a prevalent disease in North America and Eurasia <ref name="Cordes">PMID: 15711564</ref>. In order for ''B. burgdorferi'' to survive in its host, it evades the host's immune system through the use of complement regulator-acquiring surface proteins. One such protein responsible for a successful initial infection is ''Borrelia burgdorferi'' complement regulator-acquiring surface protein 1, or BbCRASP-1 <ref name="Bykowski">PMID: 17562769</ref>. Because BbCRASP-1 binds host complement regulators to the spirochete's outer surface, ''B. burgdorferi'' remains undetected within the host <ref name="Bykowski">PMID: 17562769</ref>. BbCRASP-1 specifically binds to complement Factor H (FH) and Factor H-like proteins (FHL-1), which are responsible for the host's immune response and detection of pathogens <ref name="Kraiczy">PMID: 14607842</ref>. Recently, it was found that BbCRASP-1 binds to several other proteins in the extra cellular matrix of a human cell.

== '''Function''' ==

BbCRASP-1 can be found on the outer layer of the Lyme disease spirochete and is essential for the infiltration of the spirochete into the host <ref name="Bykowski">PMID: 17562769</ref>. BbCRASP-1 provides resistance for the spirochete against the host's complementary immune system as well as spreading of the spirochete within the host.

=== '''Host Immune Response Evasion''' ===

BbCRASP-1 has an affinity for Factor H and Factor H-like proteins. Therefore, Factor H binds to BbCRASP-1, which is bound to the outer surface of the spirochete. Because there are multiple BbCRASP-1 proteins on the spirochete, the spirochete is coated with [http://www.uniprot.org/uniprot/CFAH_HUMAN Factor H] and effectively able to infiltrate the host and go undetected in the host's plasma<ref name="Bykowski">PMID: 17562769</ref>.

=== '''Relation to the Extra Cellular Matrix''' ===

Recently it was found that BbCRASP-1 not only binds to FH and FHL-1 proteins, but it also binds to several other human ligands such as [http://www.uniprot.org/uniprot/BMP2_HUMAN BMP-2] and Extra cellular matrix ligands Collagen I, Collagen III, Collagen IV, fibronectin, laminin, and plasminogen <ref name"Hallstrom">PMID: 20565259</ref>. As a result of this new finding, BbCRASP-1 is said to not only advocate the bypassing of the complementary immune system, but facilitate the dissemination of "B. burgdorferi" within the host's tissues <ref name"Hallström">PMID: 20565259</ref>. Binding to the ECM of a host is common strategy used by pathogens to acquire contact within the host <ref name"Burgmann">PMID: 19118218</ref><ref name"Hallström">PMID: 16785539</ref>.

<applet load='BBCRASP-12' size='250' frame='true' align='right' caption='BbCRASP-1' scene='Insert optional scene name here' />

== '''Structure''' ==

In nature, BbCRASP-1 exists as a homodimer bound to the spirochete's surface <ref name="Cordes">PMID: 15711564</ref>. Researchers confirmed this by viewing the presence of pieces of the dimer in solution <ref name="Cordes">PMID: 15711564</ref>. They viewed the results through analytical ultracentrifugation and saw that dimeric crystals formed. If its dimeric state is threatened, BbCRASP-1 would not be able to function.

=== '''Importance of the C-terminus''' ===

Sequences of high conservation in the C-terminal regions of the protein’s monomers, <scene name='SB2013_L01gr6/C-terminus/1'>residues 241 to 250</scene> , were of interest as a potential binding site <ref name="Cordes">PMID: 15711564</ref>. Previous studies showed that deletion of these sites caused a complete inability of BbCRASP-1 to bind FH and FHL-1 regulators <ref name="Kraiczy">PMID: 14607842</ref>. Scientists determined whether the role of the C-terminus region was in maintaining structure or directly functioning as a binding site by mutating <scene name='SB2013_L01gr6/Leucine_246/1'>leucine 246</scene> in the C-terminus region of the dimer to aspartate <ref name="Cordes">PMID: 15711564</ref>. Both the C-terminally truncated and mutated BbCRASP-1 proteins lost their ability to dimerize, inhibiting them from binding to their host’s regulatory factors. It was then concluded that the C-terminus is a structurally sensitive region rather than a direct binding site <ref name="Cordes">PMID: 15711564</ref>. The C-terminus one monomer lies against the <scene name='SB2013_L01gr6/N-terminal_helix/1'>N-terminal half of the helix</scene> of the other and holds the <scene name='SB2013_L01gr6/Monomers/1'>two monomers</scene> in place <ref name="Cordes">PMID: 15711564</ref>.

=== '''Other Potential Binding Sites''' ===

Additional studies were done to investigate the FH and FHL-1 binding sites on the protein. As with previous research, areas of high conservation were investigated due to their relationship with upholding the structure and function of the protein <ref name="CordesF">PMID: 16530476</ref>. Researchers examined highly conserved areas of amino acid sequences along the <scene name='SB2013_L01gr6/Pocket_region/3'>cleft region</scene> of the protein. They saw that the majority of these regions clustered on a highly-exposed region of the protein. A binding site in this region would be probable because this area allows more contact with the regulator proteins and would aid in further evasion of the immune system by shielding the binding domain from potential detection <ref name="CordesF">PMID: 16530476</ref>.

== References ==

<references />

Complement Regulator-Acquiring Surface Protein

2013-05-06T01:38:34Z

Dipanshu Walia:

<Structure load='1w33' size='250' frame='true' align='right' caption='BbCRASP-1' scene='Insert optional scene name here' />

== '''Introduction''' ==

Lyme disease is caused by the [http://en.wikipedia.org/wiki/Spirochaete spirochete] ''Borrelia burgdorferi'', and is transferred into vertebrate hosts by zoonotic vectors such as ''Ixodes'' ticks <ref name="Bykowski">PMID: 17562769</ref>. There are thousands of cases of Lyme disease reported each year, making it a prevalent disease in North America and Eurasia <ref name="Cordes">PMID: 15711564</ref>. In order for ''B. burgdorferi'' to survive in its host, it evades the host's immune system through the use of complement regulator-acquiring surface proteins. One such protein responsible for a successful initial infection is ''Borrelia burgdorferi'' complement regulator-acquiring surface protein 1, or BbCRASP-1 <ref name="Bykowski">PMID: 17562769</ref>. Because BbCRASP-1 binds host complement regulators to the spirochete's outer surface, ''B. burgdorferi'' remains undetected within the host <ref name="Bykowski">PMID: 17562769</ref>. BbCRASP-1 specifically binds to complement Factor H (FH) and Factor H-like proteins (FHL-1), which are responsible for the host's immune response and detection of pathogens <ref name="Kraiczy">PMID: 14607842</ref>. Recently, it was found that BbCRASP-1 binds to several other proteins in the extra cellular matrix of a human cell.

== '''Function''' ==

BbCRASP-1 can be found on the outer layer of the Lyme disease spirochete and is essential for the infiltration of the spirochete into the host <ref name="Bykowski">PMID: 17562769</ref>. BbCRASP-1 provides resistance for the spirochete against the host's complementary immune system as well as spreading of the spirochete within the host.

=== '''Host Immune Response Evasion''' ===

BbCRASP-1 has an affinity for Factor H and Factor H-like proteins. Therefore, Factor H binds to BbCRASP-1, which is bound to the outer surface of the spirochete. Because there are multiple BbCRASP-1 proteins on the spirochete, the spirochete is coated with [http://www.uniprot.org/uniprot/CFAH_HUMAN Factor H] and effectively able to infiltrate the host and go undetected in the host's plasma<ref name="Bykowski">PMID: 17562769</ref>.

=== '''Relation to the Extra Cellular Matrix''' ===

Recently it was found that BbCRASP-1 not only binds to FH and FHL-1 proteins, but it also binds to several other human ligands such as [http://www.uniprot.org/uniprot/BMP2_HUMAN BMP-2] and Extra cellular matrix ligands Collagen I, Collagen III, Collagen IV, fibronectin, laminin, and plasminogen <ref name"Hallstrom">PMID: 20565259</ref>. As a result of this new finding, BbCRASP-1 is said to not only advocate the bypassing of the complementary immune system, but facilitate the dissemination of "B. burgdorferi" within the host's tissues <ref name"Hallström">PMID: 20565259</ref>. Binding to the ECM of a host is common strategy used by pathogens to acquire contact within the host <ref name"Burgmann">PMID: 19118218</ref><ref name"Hallström">PMID: 16785539</ref>.

<applet load='BBCRASP-12' size='250' frame='true' align='right' caption='BbCRASP-1' scene='Insert optional scene name here' />

== '''Structure''' ==

In nature, BbCRASP-1 exists as a homodimer bound to the spirochete's surface <ref name="Cordes">PMID: 15711564</ref>. Researchers confirmed this by viewing the presence of pieces of the dimer in solution <ref name="Cordes">PMID: 15711564</ref>. They viewed the results through analytical ultracentrifugation and saw that dimeric crystals formed. If its dimeric state is threatened, BbCRASP-1 would not be able to function.

=== '''Importance of the C-terminus''' ===

Sequences of high conservation in the C-terminal regions of the protein’s monomers, <scene name='SB2013_L01gr6/C-terminus/1'>residues 241 to 250</scene> , were of interest as a potential binding site <ref name="Cordes">PMID: 15711564</ref>. Previous studies showed that deletion of these sites caused a complete inability of BbCRASP-1 to bind FH and FHL-1 regulators <ref name="Kraiczy">PMID: 14607842</ref>. Scientists determined whether the role of the C-terminus region was in maintaining structure or directly functioning as a binding site by mutating <scene name='SB2013_L01gr6/Leucine_246/1'>leucine 246</scene> in the C-terminus region of the dimer to aspartate <ref name="Cordes">PMID: 15711564</ref>. Both the C-terminally truncated and mutated BbCRASP-1 proteins lost their ability to dimerize, inhibiting them from binding to their host’s regulatory factors. It was then concluded that the C-terminus is a structurally sensitive region rather than a direct binding site <ref name="Cordes">PMID: 15711564</ref>. The C-terminus one monomer lies against the <scene name='SB2013_L01gr6/N-terminal_helix/1'>N-terminal half of the helix</scene> of the other and holds the <scene name='SB2013_L01gr6/Monomers/1'>two monomers</scene> in place <ref name="Cordes">PMID: 15711564</ref>.

=== '''Other Potential Binding Sites''' ===

Additional studies were done to investigate the FH and FHL-1 binding sites on the protein. As with previous research, areas of high conservation were investigated due to their relationship with upholding the structure and function of the protein <ref name="CordesF">PMID: 16530476</ref>. Researchers examined highly conserved areas of amino acid sequences along the <scene name='SB2013_L01gr6/Pocket_region/3'>cleft region</scene> of the protein. They saw that the majority of these regions clustered on a highly-exposed region of the protein. A binding site in this region would be probable because this area allows more contact with the regulator proteins and would aid in further evasion of the immune system by shielding the binding domain from potential detection <ref name="CordesF">PMID: 16530476</ref>.

== References ==

<references />

Complement Regulator-Acquiring Surface Protein

2013-05-05T19:46:04Z

Dipanshu Walia:

<Structure load='1w33' size='250' frame='true' align='right' caption='BbCRASP-1' scene='Insert optional scene name here' />

== '''Introduction''' ==

Lyme disease is caused by the [http://en.wikipedia.org/wiki/Spirochaete spirochete] ''Borrelia burgdorferi'', and is transferred into vertebrate hosts by zoonotic vectors such as ''Ixodes'' ticks <ref name="Bykowski">PMID: 17562769</ref>. There are thousands of cases of Lyme disease reported each year, making it a prevalent disease in North America and Eurasia <ref name="Cordes">PMID: 15711564</ref>. In order for ''B. burgdorferi'' to survive in its host, it evades the host's immune system through the use of complement regulator-acquiring surface proteins. One such protein responsible for a successful initial infection is ''Borrelia burgdorferi'' complement regulator-acquiring surface protein 1, or BbCRASP-1 <ref name="Bykowski">PMID: 17562769</ref>. Because BbCRASP-1 binds host complement regulators to the spirochete's outer surface, ''B. burgdorferi'' remains undetected within the host <ref name="Bykowski">PMID: 17562769</ref>. BbCRASP-1 specifically binds to complement Factor H (FH) and Factor H-like proteins (FHL-1), which are responsible for the host's immune response and detection of pathogens <ref name="Kraiczy">PMID: 14607842</ref>. Recently, it was found that BbCRASP-1 binds to several other proteins in the extra cellular matrix of a human cell.

== '''Function''' ==

BbCRASP-1 can be found on the outer layer of the Lyme disease spirochete and is essential for the infiltration of the spirochete into the host <ref name="Bykowski">PMID: 17562769</ref>. BbCRASP-1 provides resistance for the spirochete against the host's complementary immune system as well as spreading of the spirochete within the host.

=== '''Host Immune Response Evasion''' ===

BbCRASP-1 has an affinity for Factor H and Factor H-like proteins. Therefore, Factor H binds to BbCRASP-1, which is bound to the outer surface of the spirochete. Because there are multiple BbCRASP-1 proteins on the spirochete, the spirochete is coated with [http://www.uniprot.org/uniprot/CFAH_HUMAN Factor H] and effectively able to infiltrate the host and go undetected in the host's plasma<ref name="Bykowski">PMID: 17562769</ref>.

=== '''Relation to the Extra Cellular Matrix''' ===

Recently it was found that BbCRASP-1 not only binds to FH and FHL-1 proteins, but it also binds to several other human ligands such as [http://www.uniprot.org/uniprot/BMP2_HUMAN BMP-2] and Extra cellular matrix ligands Collagen I, Collagen III, Collagen IV, fibronectin, laminin, and plasminogen <ref name"Hallstrom">PMID: 20565259</ref>. As a result of this new finding, BbCRASP-1 is said to not only advocate the bypassing of the complementary immune system, but facilitate the dissemination of "B. burgdorferi" within the host's tissues <ref name"Hallström">PMID: 20565259</ref>. Binding to the ECM of a host is common strategy used by pathogens to acquire contact within the host <ref name"Burgmann">PMID: 19118218</ref><ref name"Hallström">PMID: 16785539</ref>.

<applet load='BBCRASP-12' size='250' frame='true' align='right' caption='BbCRASP-1' scene='Insert optional scene name here' />

== '''Structure''' ==

In nature, BbCRASP-1 exists as a homodimer bound to the spirochete's surface <ref name="Cordes">PMID: 15711564</ref>. Researchers confirmed this by viewing the presence of pieces of the dimer in solution <ref name="Cordes">PMID: 15711564</ref>. They viewed the results through analytical ultracentrifugation and saw that dimeric crystals formed. If its dimeric state is threatened, BbCRASP-1 would not be able to function.

=== '''Importance of the C-terminus''' ===

Sequences of high conservation in the C-terminal regions of the protein’s monomers, <scene name='SB2013_L01gr6/C-terminus/1'>residues 241 to 250</scene> , were of interest as a potential binding site <ref name="Cordes">PMID: 15711564</ref>. Previous studies showed that deletion of these sites caused a complete inability of BbCRASP-1 to bind FH and FHL-1 regulators <ref name="Kraiczy">PMID: 14607842</ref>. Scientists determined whether the role of the C-terminus region was in maintaining structure or directly functioning as a binding site by mutating <scene name='SB2013_L01gr6/Leucine_246/1'>leucine 246</scene> in the C-terminus region of the dimer to aspartate <ref name="Cordes">PMID: 15711564</ref>. This new polar molecule disrupted the hydrophobic interactions in the core of the C-terminal region and caused the entire structure to aggregate as functionally inert mutants. Both the C-terminally truncated and mutated BbCRASP-1 proteins lost their ability to dimerize, inhibiting them from binding to their host’s regulatory factors. It was then concluded that the C-terminus is a structurally sensitive region rather than a direct binding site <ref name="Cordes">PMID: 15711564</ref>. The C-terminus aids in the stabilization of the dimer by holding the <scene name='SB2013_L01gr6/Monomers/1'>two monomers</scene> in place. The C-terminal of one monomer lies against the <scene name='SB2013_L01gr6/N-terminal_helix/1'>N-terminal half of the helix</scene> of the other and keeps the structure together <ref name="Cordes">PMID: 15711564</ref>.

=== '''Other Potential Binding Sites''' ===

Additional studies were done to investigate the FH and FHL-1 binding sites on the protein. As with previous research, areas of high conservation were investigated due to their relationship with upholding the structure and function of the protein <ref name="CordesF">PMID: 16530476</ref>. Researchers examined highly conserved areas of amino acid sequences along the <scene name='SB2013_L01gr6/Pocket_region/1'>cleft region</scene> of the protein. They saw that the majority of these regions clustered on a highly-exposed region of the protein. A binding site in this region would be probable because this area allows more contact with the regulator proteins and would aid in further evasion of the immune system by shielding the binding domain from potential detection <ref name="CordesF">PMID: 16530476</ref>.

=== References ===

<references />

Complement Regulator-Acquiring Surface Protein

2013-05-05T19:45:05Z

Dipanshu Walia:

<Structure load='1w33' size='250' frame='true' align='right' caption='BbCRASP-1' scene='Insert optional scene name here' />

== '''Introduction''' ==

Lyme disease is caused by the [http://en.wikipedia.org/wiki/Spirochaete spirochete] ''Borrelia burgdorferi'', and is transferred into vertebrate hosts by zoonotic vectors such as ''Ixodes'' ticks <ref name="Bykowski">PMID: 17562769</ref>. There are thousands of cases of Lyme disease reported each year, making it a prevalent disease in North America and Eurasia <ref name="Cordes">PMID: 15711564</ref>. In order for ''B. burgdorferi'' to survive in its host, it evades the host's immune system through the use of complement regulator-acquiring surface proteins. One such protein responsible for a successful initial infection is ''Borrelia burgdorferi'' complement regulator-acquiring surface protein 1, or BbCRASP-1 <ref name="Bykowski">PMID: 17562769</ref>. Because BbCRASP-1 binds host complement regulators to the spirochete's outer surface, ''B. burgdorferi'' remains undetected within the host <ref name="Bykowski">PMID: 17562769</ref>. BbCRASP-1 specifically binds to complement Factor H (FH) and Factor H-like proteins (FHL-1), which are responsible for the host's immune response and detection of pathogens <ref name="Kraiczy">PMID: 14607842</ref>. Recently, it was found that BbCRASP-1 binds to several other proteins in the extra cellular matrix of a human cell.

== '''Function''' ==

BbCRASP-1 can be found on the outer layer of the Lyme disease spirochete and is essential for the infiltration of the spirochete into the host <ref name="Bykowski">PMID: 17562769</ref>. BbCRASP-1 provides resistance for the spirochete against the host's complementary immune system as well as spreading of the spirochete within the host.

=== '''Host Immune Response Evasion''' ===

BbCRASP-1 has an affinity for Factor H and Factor H-like proteins. Therefore, Factor H binds to BbCRASP-1, which is bound to the outer surface of the spirochete. Because there are multiple BbCRASP-1 proteins on the spirochete, the spirochete is coated with [http://www.uniprot.org/uniprot/CFAH_HUMAN Factor H] and effectively able to infiltrate the host and go undetected in the host's plasma<ref name="Bykowski">PMID: 17562769</ref>.

=== '''Relation to the Extra Cellular Matrix''' ===

Recently it was found that BbCRASP-1 not only binds to FH and FHL-1 proteins, but it also binds to several other human ligands such as [http://www.uniprot.org/uniprot/BMP2_HUMAN BMP-2] and Extra cellular matrix ligands Collagen I, Collagen III, Collagen IV, fibronectin, laminin, and plasminogen <ref name"Hallstrom">PMID: 20565259</ref>. As a result of this new finding, BbCRASP-1 is said to not only advocate the bypassing of the complementary immune system, but facilitate the dissemination of "B. burgdorferi" within the host's tissues <ref name"Hallström">PMID: 20565259</ref>. Binding to the ECM of a host is common strategy used by pathogens to acquire contact within the host. <ref name"Burgmann">PMID: 19118218</ref> <ref name"Hallström">PMID: 16785539</ref>.

<applet load='BBCRASP-12' size='250' frame='true' align='right' caption='BbCRASP-1' scene='Insert optional scene name here' />

== '''Structure''' ==

In nature, BbCRASP-1 exists as a homodimer bound to the spirochete's surface <ref name="Cordes">PMID: 15711564</ref>. Researchers confirmed this by viewing the presence of pieces of the dimer in solution <ref name="Cordes">PMID: 15711564</ref>. They viewed the results through analytical ultracentrifugation and saw that dimeric crystals formed. If its dimeric state is threatened, BbCRASP-1 would not be able to function.

=== '''Importance of the C-terminus''' ===

Sequences of high conservation in the C-terminal regions of the protein’s monomers, <scene name='SB2013_L01gr6/C-terminus/1'>residues 241 to 250</scene> , were of interest as a potential binding site <ref name="Cordes">PMID: 15711564</ref>. Previous studies showed that deletion of these sites caused a complete inability of BbCRASP-1 to bind FH and FHL-1 regulators <ref name="Kraiczy">PMID: 14607842</ref>. Scientists determined whether the role of the C-terminus region was in maintaining structure or directly functioning as a binding site by mutating <scene name='SB2013_L01gr6/Leucine_246/1'>leucine 246</scene> in the C-terminus region of the dimer to aspartate <ref name="Cordes">PMID: 15711564</ref>. This new polar molecule disrupted the hydrophobic interactions in the core of the C-terminal region and caused the entire structure to aggregate as functionally inert mutants. Both the C-terminally truncated and mutated BbCRASP-1 proteins lost their ability to dimerize, inhibiting them from binding to their host’s regulatory factors. It was then concluded that the C-terminus is a structurally sensitive region rather than a direct binding site <ref name="Cordes">PMID: 15711564</ref>. The C-terminus aids in the stabilization of the dimer by holding the <scene name='SB2013_L01gr6/Monomers/1'>two monomers</scene> in place. The C-terminal of one monomer lies against the <scene name='SB2013_L01gr6/N-terminal_helix/1'>N-terminal half of the helix</scene> of the other and keeps the structure together <ref name="Cordes">PMID: 15711564</ref>.

=== '''Other Potential Binding Sites''' ===

Additional studies were done to investigate the FH and FHL-1 binding sites on the protein. As with previous research, areas of high conservation were investigated due to their relationship with upholding the structure and function of the protein <ref name="CordesF">PMID: 16530476</ref>. Researchers examined highly conserved areas of amino acid sequences along the <scene name='SB2013_L01gr6/Pocket_region/1'>cleft region</scene> of the protein. They saw that the majority of these regions clustered on a highly-exposed region of the protein. A binding site in this region would be probable because this area allows more contact with the regulator proteins and would aid in further evasion of the immune system by shielding the binding domain from potential detection <ref name="CordesF">PMID: 16530476</ref>.

=== References ===

<references />

Complement Regulator-Acquiring Surface Protein

2013-05-05T02:08:49Z

Dipanshu Walia:

<Structure load='1w33' size='250' frame='true' align='right' caption='BbCRASP-1' scene='Insert optional scene name here' />

== '''Introduction''' ==

Lyme disease is caused by the spirochete ''Borrelia burgdorferi'', and is transferred into vertebrate hosts by zoonotic vectors such as ''Ixodes'' ticks <ref name="Bykowski">PMID: 17562769</ref>. There are thousands of cases of Lyme disease reported each year, making it a prevalent disease in North America and Eurasia <ref name="Cordes">PMID: 15711564</ref>. In order for ''B. burgdorferi'' to survive in its host, it evades the host's immune system through the use of complement regulator-acquiring surface proteins. One such protein responsible for a successful initial infection is ''Borrelia burgdorferi'' complement regulator-acquiring surface protein 1, or BbCRASP-1 <ref name="Bykowski">PMID: 17562769</ref>. Because BbCRASP-1 binds host complement regulators to the spirochete's outer surface, ''B. burgdorferi'' remains undetected within the host <ref name="Bykowski">PMID: 17562769</ref>. BbCRASP-1 specifically binds to complement Factor H (FH) and Factor H-like proteins (FHL-1), which are responsible for the host's immune response and detection of pathogens <ref name="Kraiczy">PMID: 14607842</ref>. Recently, it was found that BbCRASP-1 binds to several other proteins in the extra cellular matrix of a human cell.

== '''Function''' ==

BbCRASP-1 can be found on the outer layer of the Lyme disease spirochete and is essential for the infiltration of the spirochete into the host <ref name="Bykowski">PMID: 17562769</ref>. BbCRASP-1 provides resistance for the spirochete against the host's complementary immune system as well as spreading of the spirochete within the host.

=== '''Host Immune Response Evasion''' ===

BbCRASP-1 has an affinity for Factor H and Factor H-like proteins. Therefore, Factor H binds to BbCRASP-1, which is bound to the outer surface of the spirochete. Because there are multiple BbCRASP-1 proteins on the spirochete, the spirochete is coated with [http://www.uniprot.org/uniprot/CFAH_HUMAN Factor H] and effectively able to infiltrate the host and go undetected in the host's plasma<ref name="Bykowski">PMID: 17562769</ref>.

=== '''Relation to the Extra Cellular Matrix''' ===

Recently it was found that BbCRASP-1 not only binds to FH and FHL-1 proteins, but it also binds to several other human ligands such as [http://www.uniprot.org/uniprot/BMP2_HUMAN BMP-2] and Extra cellular matrix ligands Collagen I, Collagen III, Collagen IV, fibronectin, laminin, and plasminogen <ref name"Hallstrom">PMID: 20565259</ref>. As a result of this new finding, BbCRASP-1 is said to advocate the bypassing of the complementary immune system in addition to the pathogenesis of Lyme disease. BbCRASP-1 facilitates binding of “Borrelia burgdoferi” to human cells and tissues, which helps spread the infection <ref name"Hallstrom">PMID: 20565259</ref>.

<applet load='BBCRASP-12' size='250' frame='true' align='right' caption='BbCRASP-1' scene='Insert optional scene name here' />

== '''Structure''' ==

In nature, BbCRASP-1 exists as a homodimer bound to the spirochete's surface <ref name="Cordes">PMID: 15711564</ref>. Researchers confirmed this by viewing the presence of pieces of the dimer in solution <ref name="Cordes">PMID: 15711564</ref>. They viewed the results through analytical ultracentrifugation and saw that dimeric crystals formed. If its dimeric state is threatened, BbCRASP-1 would not be able to function.

=== '''Importance of the C-terminus''' ===

Sequences of high conservation in the C-terminal regions of the protein’s monomers, <scene name='SB2013_L01gr6/C-terminus/1'>residues 241 to 250</scene> , were of interest as a potential binding site <ref name="Cordes">PMID: 15711564</ref>. Previous studies showed that deletion of these sites caused a complete inability of BbCRASP-1 to bind FH and FHL-1 regulators <ref name="Kraiczy">PMID: 14607842</ref>. Scientists determined whether the role of the C-terminus region was in maintaining structure or directly functioning as a binding site by mutating <scene name='SB2013_L01gr6/Leucine_246/1'>leucine 246</scene> in the C-terminus region of the dimer to aspartate <ref name="Cordes">PMID: 15711564</ref>. This new polar molecule disrupted the hydrophobic interactions in the core of the C-terminal region and caused the entire structure to aggregate as functionally inert mutants. Both the C-terminally truncated and mutated BbCRASP-1 proteins lost their ability to dimerize, inhibiting them from binding to their host’s regulatory factors. It was then concluded that the C-terminus is a structurally sensitive region rather than a direct binding site <ref name="Cordes">PMID: 15711564</ref>. The C-terminus aids in the stabilization of the dimer by holding the <scene name='SB2013_L01gr6/Monomers/1'>two monomers</scene> in place. The C-terminal of one monomer lies against the <scene name='SB2013_L01gr6/N-terminal_helix/1'>N-terminal half of the helix</scene> of the other and keeps the structure together <ref name="Cordes">PMID: 15711564</ref>.

=== '''Other Potential Binding Sites''' ===

Additional studies were done to investigate the FH and FHL-1 binding sites on the protein. As with previous research, areas of high conservation were investigated due to their relationship with upholding the structure and function of the protein <ref name="CordesF">PMID: 16530476</ref>. Researchers examined highly conserved areas of amino acid sequences along the <scene name='SB2013_L01gr6/Pocket_region/1'>cleft region</scene> of the protein. They saw that the majority of these regions clustered on a highly-exposed region of the protein. A binding site in this region would be probable because this area allows more contact with the regulator proteins and would aid in further evasion of the immune system by shielding the binding domain from potential detection <ref name="CordesF">PMID: 16530476</ref>.

=== References ===

<references />

Complement Regulator-Acquiring Surface Protein

2013-05-05T02:02:53Z

Dipanshu Walia:

<Structure load='1w33' size='250' frame='true' align='right' caption='BbCRASP-1' scene='Insert optional scene name here' />

== '''Introduction''' ==

Lyme disease is caused by the spirochete ''Borrelia burgdorferi'', and is transferred into vertebrate hosts by zoonotic vectors such as ''Ixodes'' ticks <ref name="Bykowski">PMID: 17562769</ref>. There are thousands of cases of Lyme disease reported each year, making it a prevalent disease in North America and Eurasia <ref name="Cordes">PMID: 15711564</ref>. In order for ''B. burgdorferi'' to survive in its host, it evades the host's immune system through the use of complement regulator-acquiring surface proteins. One such protein responsible for a successful initial infection is ''Borrelia burgdorferi'' complement regulator-acquiring surface protein 1, or BbCRASP-1 <ref name="Bykowski">PMID: 17562769</ref>. Because BbCRASP-1 binds host complement regulators to the spirochete's outer surface, ''B. burgdorferi'' remains undetected within the host <ref name="Bykowski">PMID: 17562769</ref>. BbCRASP-1 specifically binds to complement Factor H (FH) and Factor H-like proteins (FHL-1), which are responsible for the host's immune response and detection of pathogens <ref name="Kraiczy">PMID: 14607842</ref>. Recently, it was found that BbCRASP-1 binds to several other proteins in the extra cellular matrix of a human cell.

== '''Function''' ==

BbCRASP-1 can be found on the outer layer of the Lyme disease spirochete and is essential for the infiltration of the spirochete into the host <ref name="Bykowski">PMID: 17562769</ref>. BbCRASP-1 provides resistance for the spirochete against the host's complementary immune system as well as spreading of the spirochete within the host.

=== '''Host Immune Response Evasion''' ===

BbCRASP-1 has an affinity for Factor H and Factor H-like proteins. Therefore, Factor H binds to BbCRASP-1, which is bound to the outer surface of the spirochete. Because there are multiple BbCRASP-1 proteins on the spirochete, the spirochete is coated with [http://www.uniprot.org/uniprot/CFAH_HUMAN Factor H] and effectively able to infiltrate the host and go undetected in the host's plasma<ref name="Bykowski">PMID: 17562769</ref>.

=== '''Relation to the Extra Cellular Matrix''' ===

Recently it was found that BbCRASP-1 not only binds to FH and FHL-1 proteins, but it also binds to several other human ligands such as [http://www.uniprot.org/uniprot/BMP2_HUMAN BMP-2] and Extra cellular matrix ligands Collagen I, Collagen III, Collagen IV, fibronectin, laminin, and plasminogen <ref name"Hallstrom">PMID: 20565259</ref>. As a result of this new finding, BbCRASP-1 is said to advocate the bypassing of the complementary immune system in addition to the pathogenesis of Lyme disease. BbCRASP-1 facilitates binding of “Borrelia burgdoferi” to human cells and tissues, which helps spread the infection <ref name"Hallstrom">PMID: 20565259</ref>.

<applet load='BBCRASP-12' size='250' frame='true' align='right' caption='BbCRASP-1' scene='Insert optional scene name here' />

== '''Structure''' ==

In nature, BbCRASP-1 exists as a homodimer bound to the spirochete's surface <ref name="Cordes">PMID: 15711564</ref>. Researchers confirmed this by viewing the presence of pieces of the dimer in solution <ref name="Cordes">PMID: 15711564</ref>. They viewed the results through analytical ultracentrifugation and saw that dimeric crystals formed. If its dimeric state is threatened, BbCRASP-1 would not be able to function.

=== '''Importance of the C-terminus''' ===

Sequences of high conservation in the C-terminal regions of the protein’s monomers, <scene name='SB2013_L01gr6/C-terminus/1'>residues 241 to 250</scene> , were of interest as a potential binding site <ref name="Cordes">PMID: 15711564</ref>. Previous studies showed that deletion of these sites caused a complete inability of BbCRASP-1 to bind FH and FHL-1 regulators <ref name="Kraiczy">PMID: 14607842</ref>. Scientists determined whether the role of the C-terminus region was in maintaining structure or directly functioning as a binding site by mutating <scene name='SB2013_L01gr6/Leucine_246/1'>leucine 246</scene> in the C-terminus region of the dimer to aspartate <ref name="Cordes">PMID: 15711564</ref>. This new polar molecule disrupted the hydrophobic interactions in the core of the C-terminal region and caused the entire structure to aggregate as functionally inert mutants. Both the C-terminally truncated and mutated BbCRASP-1 proteins lost their ability to dimerize, inhibiting them from binding to their host’s regulatory factors. It was then concluded that the C-terminus is a structurally sensitive region rather than a direct binding site <ref name="Cordes">PMID: 15711564</ref>. The C-terminus aids in the stabilization of the dimer by holding the <scene name='SB2013_L01gr6/Monomers/1'>two monomers</scene> in place. The C-terminal of one monomer lies against the <scene name='SB2013_L01gr6/N-terminal_helix/1'>N-terminal half of the helix</scene> of the other and keeps the structure together <ref name="Cordes">PMID: 15711564</ref>.

=== '''Other Potential Binding Sites''' ===

Additional studies were done to investigate the FH and FHL-1 binding sites on the protein. As with previous research, areas of high conservation were investigated due to their relationship with upholding the structure and function of the protein <ref name="CordesF">PMID: 16530476</ref>. Researchers examined highly conserved areas of amino acid sequences along the <scene name='SB2013_L01gr6/Pocket_region/1'>cleft region</scene> of the protein. They saw that the majority of these regions clustered on a highly-exposed region of the protein.

=== References ===

<references />

Complement Regulator-Acquiring Surface Protein

2013-05-05T02:02:24Z

Dipanshu Walia:

<Structure load='1w33' size='250' frame='true' align='right' caption='BbCRASP-1' scene='Insert optional scene name here' />

== '''Introduction''' ==

Lyme disease is caused by the spirochete ''Borrelia burgdorferi'', and is transferred into vertebrate hosts by zoonotic vectors such as ''Ixodes'' ticks <ref name="Bykowski">PMID: 17562769</ref>. There are thousands of cases of Lyme disease reported each year, making it a prevalent disease in North America and Eurasia <ref name="Cordes">PMID: 15711564</ref>. In order for ''B. burgdorferi'' to survive in its host, it evades the host's immune system through the use of complement regulator-acquiring surface proteins. One such protein responsible for a successful initial infection is ''Borrelia burgdorferi'' complement regulator-acquiring surface protein 1, or BbCRASP-1 <ref name="Bykowski">PMID: 17562769</ref>. Because BbCRASP-1 binds host complement regulators to the spirochete's outer surface, ''B. burgdorferi'' remains undetected within the host <ref name="Bykowski">PMID: 17562769</ref>. BbCRASP-1 specifically binds to complement Factor H (FH) and Factor H-like proteins (FHL-1), which are responsible for the host's immune response and detection of pathogens <ref name="Kraiczy">PMID: 14607842</ref>. Recently, it was found that BbCRASP-1 binds to several other proteins in the extra cellular matrix of a human cell.

== '''Function''' ==

BbCRASP-1 can be found on the outer layer of the Lyme disease spirochete and is essential for the infiltration of the spirochete into the host <ref name="Bykowski">PMID: 17562769</ref>. BbCRASP-1 provides resistance for the spirochete against the host's complementary immune system as well as spreading of the spirochete within the host.

=== '''Host Immune Response Evasion''' ===

BbCRASP-1 has an affinity for Factor H and Factor H-like proteins. Therefore, Factor H binds to BbCRASP-1, which is bound to the outer surface of the spirochete. Because there are multiple BbCRASP-1 proteins on the spirochete, the spirochete is coated with [http://www.uniprot.org/uniprot/CFAH_HUMAN Factor H] and effectively able to infiltrate the host and go undetected in the host's plasma<ref name="Bykowski">PMID: 17562769</ref>.

=== '''Relation to the Extra Cellular Matrix''' ===

Recently it was found that BbCRASP-1 not only binds to FH and FHL-1 proteins, but it also binds to several other human ligands such as [http://www.uniprot.org/uniprot/BMP2_HUMAN BMP-2] and Extra cellular matrix ligands Collagen I, Collagen III, Collagen IV, fibronectin, laminin, and plasminogen <ref name"Hallstrom">PMID: 20565259</ref>. As a result of this new finding, BbCRASP-1 is said to advocate the bypassing of the complementary immune system in addition to the pathogenesis of Lyme disease. BbCRASP-1 facilitates binding of “Borrelia burgdoferi” to human cells and tissues, which helps spread the infection (Hallstrom et al. 2010).

<applet load='BBCRASP-12' size='250' frame='true' align='right' caption='BbCRASP-1' scene='Insert optional scene name here' />

== '''Structure''' ==

In nature, BbCRASP-1 exists as a homodimer bound to the spirochete's surface <ref name="Cordes">PMID: 15711564</ref>. Researchers confirmed this by viewing the presence of pieces of the dimer in solution <ref name="Cordes">PMID: 15711564</ref>. They viewed the results through analytical ultracentrifugation and saw that dimeric crystals formed. If its dimeric state is threatened, BbCRASP-1 would not be able to function.

=== '''Importance of the C-terminus''' ===

Sequences of high conservation in the C-terminal regions of the protein’s monomers, <scene name='SB2013_L01gr6/C-terminus/1'>residues 241 to 250</scene> , were of interest as a potential binding site <ref name="Cordes">PMID: 15711564</ref>. Previous studies showed that deletion of these sites caused a complete inability of BbCRASP-1 to bind FH and FHL-1 regulators <ref name="Kraiczy">PMID: 14607842</ref>. Scientists determined whether the role of the C-terminus region was in maintaining structure or directly functioning as a binding site by mutating <scene name='SB2013_L01gr6/Leucine_246/1'>leucine 246</scene> in the C-terminus region of the dimer to aspartate <ref name="Cordes">PMID: 15711564</ref>. This new polar molecule disrupted the hydrophobic interactions in the core of the C-terminal region and caused the entire structure to aggregate as functionally inert mutants. Both the C-terminally truncated and mutated BbCRASP-1 proteins lost their ability to dimerize, inhibiting them from binding to their host’s regulatory factors. It was then concluded that the C-terminus is a structurally sensitive region rather than a direct binding site <ref name="Cordes">PMID: 15711564</ref>. The C-terminus aids in the stabilization of the dimer by holding the <scene name='SB2013_L01gr6/Monomers/1'>two monomers</scene> in place. The C-terminal of one monomer lies against the <scene name='SB2013_L01gr6/N-terminal_helix/1'>N-terminal half of the helix</scene> of the other and keeps the structure together <ref name="Cordes">PMID: 15711564</ref>.

=== '''Other Potential Binding Sites''' ===

Additional studies were done to investigate the FH and FHL-1 binding sites on the protein. As with previous research, areas of high conservation were investigated due to their relationship with upholding the structure and function of the protein <ref name="CordesF">PMID: 16530476</ref>. Researchers examined highly conserved areas of amino acid sequences along the <scene name='SB2013_L01gr6/Pocket_region/1'>cleft region</scene> of the protein. They saw that the majority of these regions clustered on a highly-exposed region of the protein.

=== References ===

<references />

Complement Regulator-Acquiring Surface Protein

2013-05-05T01:59:37Z

Dipanshu Walia:

<Structure load='1w33' size='250' frame='true' align='right' caption='BbCRASP-1' scene='Insert optional scene name here' />

== '''Introduction''' ==

Lyme disease is caused by the spirochete ''Borrelia burgdorferi'', and is transferred into vertebrate hosts by zoonotic vectors such as ''Ixodes'' ticks <ref name="Bykowski">PMID: 17562769</ref>. There are thousands of cases of Lyme disease reported each year, making it a prevalent disease in North America and Eurasia <ref name="Cordes">PMID: 15711564</ref>. In order for ''B. burgdorferi'' to survive in its host, it evades the host's immune system through the use of complement regulator-acquiring surface proteins. One such protein responsible for a successful initial infection is ''Borrelia burgdorferi'' complement regulator-acquiring surface protein 1, or BbCRASP-1 <ref name="Bykowski">PMID: 17562769</ref>. Because BbCRASP-1 binds host complement regulators to the spirochete's outer surface, ''B. burgdorferi'' remains undetected within the host <ref name="Bykowski">PMID: 17562769</ref>. BbCRASP-1 specifically binds to complement Factor H (FH) and Factor H-like proteins (FHL-1), which are responsible for the host's immune response and detection of pathogens <ref name="Kraiczy">PMID: 14607842</ref>. Recently, it was found that BbCRASP-1 binds to several other proteins in the extra cellular matrix of a human cell.

== '''Function''' ==

BbCRASP-1 can be found on the outer layer of the Lyme disease spirochete and is essential for the infiltration of the spirochete into the host <ref name="Bykowski">PMID: 17562769</ref>. BbCRASP-1 provides resistance for the spirochete against the host's complementary immune system as well as spreading of the spirochete within the host.

=== '''Host Immune Response Evasion''' ===

BbCRASP-1 has an affinity for Factor H and Factor H-like proteins. Therefore, Factor H binds to BbCRASP-1, which is bound to the outer surface of the spirochete. Because there are multiple BbCRASP-1 proteins on the spirochete, the spirochete is coated with [http://www.uniprot.org/uniprot/CFAH_HUMAN Factor H] and effectively able to infiltrate the host and go undetected in the host's plasma<ref name="Bykowski">PMID: 17562769</ref>.

=== '''Relation to the Extra Cellular Matrix''' ===

Recently it was found that BbCRASP-1 not only binds to FH and FHL-1 proteins, but it also binds to several other human ligands such as [http://www.uniprot.org/uniprot/BMP2_HUMAN BMP-2] and Extra cellular matrix ligands Collagen I, Collagen III, Collagen IV, fibronectin, laminin, and plasminogen (Hallstrom et al. 2010). As a result of this new finding, BbCRASP-1 is said to advocate the bypassing of the complementary immune system in addition to the pathogenesis of Lyme disease. BbCRASP-1 facilitates binding of “Borrelia burgdoferi” to human cells and tissues, which helps spread the infection (Hallstrom et al. 2010).

<applet load='BBCRASP-12' size='250' frame='true' align='right' caption='BbCRASP-1' scene='Insert optional scene name here' />

== '''Structure''' ==

In nature, BbCRASP-1 exists as a homodimer bound to the spirochete's surface <ref name="Cordes">PMID: 15711564</ref>. Researchers confirmed this by viewing the presence of pieces of the dimer in solution <ref name="Cordes">PMID: 15711564</ref>. They viewed the results through analytical ultracentrifugation and saw that dimeric crystals formed. If its dimeric state is threatened, BbCRASP-1 would not be able to function.

=== '''Importance of the C-terminus''' ===

Sequences of high conservation in the C-terminal regions of the protein’s monomers, <scene name='SB2013_L01gr6/C-terminus/1'>residues 241 to 250</scene> , were of interest as a potential binding site <ref name="Cordes">PMID: 15711564</ref>. Previous studies showed that deletion of these sites caused a complete inability of BbCRASP-1 to bind FH and FHL-1 regulators <ref name="Kraiczy">PMID: 14607842</ref>. Scientists determined whether the role of the C-terminus region was in maintaining structure or directly functioning as a binding site by mutating <scene name='SB2013_L01gr6/Leucine_246/1'>leucine 246</scene> in the C-terminus region of the dimer to aspartate <ref name="Cordes">PMID: 15711564</ref>. This new polar molecule disrupted the hydrophobic interactions in the core of the C-terminal region and caused the entire structure to aggregate as functionally inert mutants. Both the C-terminally truncated and mutated BbCRASP-1 proteins lost their ability to dimerize, inhibiting them from binding to their host’s regulatory factors. It was then concluded that the C-terminus is a structurally sensitive region rather than a direct binding site <ref name="Cordes">PMID: 15711564</ref>. The C-terminus aids in the stabilization of the dimer by holding the <scene name='SB2013_L01gr6/Monomers/1'>two monomers</scene> in place. The C-terminal of one monomer lies against the <scene name='SB2013_L01gr6/N-terminal_helix/1'>N-terminal half of the helix</scene> of the other and keeps the structure together <ref name="Cordes">PMID: 15711564</ref>.

=== '''Other Potential Binding Sites''' ===

Additional studies were done to investigate the FH and FHL-1 binding sites on the protein. As with previous research, areas of high conservation were investigated due to their relationship with upholding the structure and function of the protein <ref name="Cordes 06">PMID: 16530476</ref>. Researchers examined highly conserved areas of amino acid sequences along the <scene name='SB2013_L01gr6/Pocket_region/1'>cleft region</scene> of the protein. They saw that the majority of these regions clustered on a highly-exposed region of the protein.

=== References ===

<references />

Complement Regulator-Acquiring Surface Protein

2013-05-05T01:58:04Z

Dipanshu Walia:

<Structure load='1w33' size='250' frame='true' align='right' caption='BbCRASP-1' scene='Insert optional scene name here' />

== '''Introduction''' ==

Lyme disease is caused by the spirochete ''Borrelia burgdorferi'', and is transferred into vertebrate hosts by zoonotic vectors such as ''Ixodes'' ticks <ref name="Bykowski">PMID: 17562769</ref>. There are thousands of cases of Lyme disease reported each year, making it a prevalent disease in North America and Eurasia <ref name="Cordes">PMID: 15711564</ref>. In order for ''B. burgdorferi'' to survive in its host, it evades the host's immune system through the use of complement regulator-acquiring surface proteins. One such protein responsible for a successful initial infection is ''Borrelia burgdorferi'' complement regulator-acquiring surface protein 1, or BbCRASP-1 <ref name="Bykowski">PMID: 17562769</ref>. Because BbCRASP-1 binds host complement regulators to the spirochete's outer surface, ''B. burgdorferi'' remains undetected within the host <ref name="Bykowski">PMID: 17562769</ref>. BbCRASP-1 specifically binds to complement Factor H (FH) and Factor H-like proteins (FHL-1), which are responsible for the host's immune response and detection of pathogens <ref name="Kraiczy">PMID: 14607842</ref>. Recently, it was found that BbCRASP-1 binds to several other proteins in the extra cellular matrix of a human cell.

== '''Function''' ==

BbCRASP-1 can be found on the outer layer of the Lyme disease spirochete and is essential for the infiltration of the spirochete into the host <ref name="Bykowski">PMID: 17562769</ref>. BbCRASP-1 provides resistance for the spirochete against the host's complementary immune system as well as spreading of the spirochete within the host.

=== '''Host Immune Response Evasion''' ===

BbCRASP-1 has an affinity for Factor H and Factor H-like proteins. Therefore, Factor H binds to BbCRASP-1, which is bound to the outer surface of the spirochete. Because there are multiple BbCRASP-1 proteins on the spirochete, the spirochete is coated with [http://www.uniprot.org/uniprot/CFAH_HUMAN Factor H] and effectively able to infiltrate the host and go undetected in the host's plasma<ref name="Bykowski">PMID: 17562769</ref>.

=== '''Relation to the Extra Cellular Matrix''' ===

Recently it was found that BbCRASP-1 not only binds to FH and FHL-1 proteins, but it also binds to several other human ligands such as [http://www.uniprot.org/uniprot/BMP2_HUMAN BMP-2] and Extra cellular matrix ligands Collagen I, Collagen III, Collagen IV, fibronectin, laminin, and plasminogen (Hallstrom et al. 2010). As a result of this new finding, BbCRASP-1 is said to advocate the bypassing of the complementary immune system in addition to the pathogenesis of Lyme disease. BbCRASP-1 facilitates binding of “Borrelia burgdoferi” to human cells and tissues, which helps spread the infection (Hallstrom et al. 2010).

<applet load='BBCRASP-12' size='250' frame='true' align='right' caption='BbCRASP-1' scene='Insert optional scene name here' />

== '''Structure''' ==

In nature, BbCRASP-1 exists as a homodimer bound to the spirochete's surface <ref name="Cordes">PMID: 15711564</ref>. Researchers confirmed this by viewing the presence of pieces of the dimer in solution <ref name="Cordes">PMID: 15711564</ref>. They viewed the results through analytical ultracentrifugation and saw that dimeric crystals formed. If its dimeric state is threatened, BbCRASP-1 would not be able to function.

=== '''Importance of the C-terminus''' ===

Sequences of high conservation in the C-terminal regions of the protein’s monomers, <scene name='SB2013_L01gr6/C-terminus/1'>residues 241 to 250</scene> , were of interest as a potential binding site <ref name="Cordes">PMID: 15711564</ref>. Previous studies showed that deletion of these sites caused a complete inability of BbCRASP-1 to bind FH and FHL-1 regulators <ref name="Kraiczy">PMID: 14607842</ref>. Scientists determined whether the role of the C-terminus region was in maintaining structure or directly functioning as a binding site by mutating <scene name='SB2013_L01gr6/Leucine_246/1'>leucine 246</scene> in the C-terminus region of the dimer to aspartate <ref name="Cordes">PMID: 15711564</ref>. This new polar molecule disrupted the hydrophobic interactions in the core of the C-terminal region and caused the entire structure to aggregate as functionally inert mutants. Both the C-terminally truncated and mutated BbCRASP-1 proteins lost their ability to dimerize, inhibiting them from binding to their host’s regulatory factors. It was then concluded that the C-terminus is a structurally sensitive region rather than a direct binding site <ref name="Cordes">PMID: 15711564</ref>. The C-terminus aids in the stabilization of the dimer by holding the <scene name='SB2013_L01gr6/Monomers/1'>two monomers</scene> in place. The C-terminal of one monomer lies against the <scene name='SB2013_L01gr6/N-terminal_helix/1'>N-terminal half of the helix</scene> of the other and keeps the structure together <ref name="Cordes">PMID: 15711564</ref>.

=== '''Other Potential Binding Sites''' ===

Additional studies were done to investigate the FH and FHL-1 binding sites on the protein. As with previous research, areas of high conservation were investigated due to their relationship with upholding the structure and function of the protein (Cordes et al. 2010). Researchers examined highly conserved areas of amino acid sequences along the <scene name='SB2013_L01gr6/Pocket_region/1'>cleft region</scene> of the protein. They saw that the majority of these regions clustered on a highly-exposed region of the protein.

=== References ===

<references />

Complement Regulator-Acquiring Surface Protein

2013-05-05T01:57:22Z

Dipanshu Walia:

<Structure load='1w33' size='250' frame='true' align='right' caption='BbCRASP-1' scene='Insert optional scene name here' />

== '''Introduction''' ==

Lyme disease is caused by the spirochete ''Borrelia burgdorferi'', and is transferred into vertebrate hosts by zoonotic vectors such as ''Ixodes'' ticks <ref name="Bykowski">PMID: 17562769</ref>. There are thousands of cases of Lyme disease reported each year, making it a prevalent disease in North America and Eurasia <ref name="Cordes">PMID: 15711564</ref>. In order for ''B. burgdorferi'' to survive in its host, it evades the host's immune system through the use of complement regulator-acquiring surface proteins. One such protein responsible for a successful initial infection is ''Borrelia burgdorferi'' complement regulator-acquiring surface protein 1, or BbCRASP-1 <ref name="Bykowski">PMID: 17562769</ref>. Because BbCRASP-1 binds host complement regulators to the spirochete's outer surface, ''B. burgdorferi'' remains undetected within the host <ref name="Bykowski">PMID: 17562769</ref>. BbCRASP-1 specifically binds to complement Factor H (FH) and Factor H-like proteins (FHL-1), which are responsible for the host's immune response and detection of pathogens <ref name="Kraiczy">PMID: 14607842</ref>. Recently, it was found that BbCRASP-1 binds to several other proteins in the extra cellular matrix of a human cell.

== '''Function''' ==

BbCRASP-1 can be found on the outer layer of the Lyme disease spirochete and is essential for the infiltration of the spirochete into the host <ref name="Bykowski">PMID: 17562769</ref>. BbCRASP-1 provides resistance for the spirochete against the host's complementary immune system as well as spreading of the spirochete within the host.

=== '''Host Immune Response Evasion''' ===

BbCRASP-1 has an affinity for Factor H and Factor H-like proteins. Therefore, Factor H binds to BbCRASP-1, which is bound to the outer surface of the spirochete. Because there are multiple BbCRASP-1 proteins on the spirochete, the spirochete is coated with [http://www.uniprot.org/uniprot/CFAH_HUMAN Factor H] and effectively able to infiltrate the host and go undetected in the host's plasma<ref name="Bykowski">PMID: 17562769</ref>.

=== '''Relation to the Extra Cellular Matrix''' ===

Recently it was found that BbCRASP-1 not only binds to FH and FHL-1 proteins, but it also binds to several other human ligands such as [http://www.uniprot.org/uniprot/BMP2_HUMAN BMP-2] and Extra cellular matrix ligands Collagen I, Collagen III, Collagen IV, fibronectin, laminin, and plasminogen (Hallstrom et al. 2010). As a result of this new finding, BbCRASP-1 is said to advocate the bypassing of the complementary immune system in addition to the pathogenesis of Lyme disease. BbCRASP-1 facilitates binding of “Borrelia burgdoferi” to human cells and tissues, which helps spread the infection (Hallstrom et al. 2010).

<applet load='BBCRASP-12' size='250' frame='true' align='right' caption='BbCRASP-1' scene='Insert optional scene name here' />

== '''Structure''' ==

In nature, BbCRASP-1 exists as a homodimer bound to the spirochete's surface <ref name="Cordes">PMID: 15711564</ref>. Researchers confirmed this by viewing the presence of pieces of the dimer in solution <ref name="Cordes">PMID: 15711564</ref>. They viewed the results through analytical ultracentrifugation and saw that dimeric crystals formed. If its dimeric state is threatened, BbCRASP-1 would not be able to function.

=== '''Importance of the C-terminus''' ===

Sequences of high conservation in the C-terminal regions of the protein’s monomers, <scene name='SB2013_L01gr6/C-terminus/1'>residues 241 to 250</scene> , were of interest as a potential binding site <ref name="Cordes">PMID: 15711564</ref>. Previous studies showed that deletion of these sites caused a complete inability of BbCRASP-1 to bind FH and FHL-1 regulators (Kraiczy P et al. 2004). Scientists determined whether the role of the C-terminus region was in maintaining structure or directly functioning as a binding site by mutating <scene name='SB2013_L01gr6/Leucine_246/1'>leucine 246</scene> in the C-terminus region of the dimer to aspartate <ref name="Cordes">PMID: 15711564</ref>. This new polar molecule disrupted the hydrophobic interactions in the core of the C-terminal region and caused the entire structure to aggregate as functionally inert mutants. Both the C-terminally truncated and mutated BbCRASP-1 proteins lost their ability to dimerize, inhibiting them from binding to their host’s regulatory factors. It was then concluded that the C-terminus is a structurally sensitive region rather than a direct binding site <ref name="Cordes">PMID: 15711564</ref>. The C-terminus aids in the stabilization of the dimer by holding the <scene name='SB2013_L01gr6/Monomers/1'>two monomers</scene> in place. The C-terminal of one monomer lies against the <scene name='SB2013_L01gr6/N-terminal_helix/1'>N-terminal half of the helix</scene> of the other and keeps the structure together <ref name="Cordes">PMID: 15711564</ref>.

=== '''Other Potential Binding Sites''' ===

Additional studies were done to investigate the FH and FHL-1 binding sites on the protein. As with previous research, areas of high conservation were investigated due to their relationship with upholding the structure and function of the protein (Cordes et al. 2010). Researchers examined highly conserved areas of amino acid sequences along the <scene name='SB2013_L01gr6/Pocket_region/1'>cleft region</scene> of the protein. They saw that the majority of these regions clustered on a highly-exposed region of the protein.

=== References ===

<references />

Complement Regulator-Acquiring Surface Protein

2013-05-05T01:55:26Z

Dipanshu Walia:

<Structure load='1w33' size='250' frame='true' align='right' caption='BbCRASP-1' scene='Insert optional scene name here' />

== '''Introduction''' ==

Lyme disease is caused by the spirochete ''Borrelia burgdorferi'', and is transferred into vertebrate hosts by zoonotic vectors such as ''Ixodes'' ticks <ref name="Bykowski">PMID: 17562769</ref>. There are thousands of cases of Lyme disease reported each year, making it a prevalent disease in North America and Eurasia <ref name="Cordes">PMID: 15711564</ref>. In order for ''B. burgdorferi'' to survive in its host, it evades the host's immune system through the use of complement regulator-acquiring surface proteins. One such protein responsible for a successful initial infection is ''Borrelia burgdorferi'' complement regulator-acquiring surface protein 1, or BbCRASP-1 <ref name="Bykowski">PMID: 17562769</ref>. Because BbCRASP-1 binds host complement regulators to the spirochete's outer surface, ''B. burgdorferi'' remains undetected within the host <ref name="Bykowski">PMID: 17562769</ref>. BbCRASP-1 specifically binds to complement Factor H (FH) and Factor H-like proteins (FHL-1), which are responsible for the host's immune response and detection of pathogens (Kraiczy et al. 2004). Recently, it was found that BbCRASP-1 binds to several other proteins in the extra cellular matrix of a human cell.

== '''Function''' ==

BbCRASP-1 can be found on the outer layer of the Lyme disease spirochete and is essential for the infiltration of the spirochete into the host <ref name="Bykowski">PMID: 17562769</ref>. BbCRASP-1 provides resistance for the spirochete against the host's complementary immune system as well as spreading of the spirochete within the host.

=== '''Host Immune Response Evasion''' ===

BbCRASP-1 has an affinity for Factor H and Factor H-like proteins. Therefore, Factor H binds to BbCRASP-1, which is bound to the outer surface of the spirochete. Because there are multiple BbCRASP-1 proteins on the spirochete, the spirochete is coated with [http://www.uniprot.org/uniprot/CFAH_HUMAN Factor H] and effectively able to infiltrate the host and go undetected in the host's plasma<ref name="Bykowski">PMID: 17562769</ref>.

=== '''Relation to the Extra Cellular Matrix''' ===

Recently it was found that BbCRASP-1 not only binds to FH and FHL-1 proteins, but it also binds to several other human ligands such as [http://www.uniprot.org/uniprot/BMP2_HUMAN BMP-2] and Extra cellular matrix ligands Collagen I, Collagen III, Collagen IV, fibronectin, laminin, and plasminogen (Hallstrom et al. 2010). As a result of this new finding, BbCRASP-1 is said to advocate the bypassing of the complementary immune system in addition to the pathogenesis of Lyme disease. BbCRASP-1 facilitates binding of “Borrelia burgdoferi” to human cells and tissues, which helps spread the infection (Hallstrom et al. 2010).

<applet load='BBCRASP-12' size='250' frame='true' align='right' caption='BbCRASP-1' scene='Insert optional scene name here' />

== '''Structure''' ==

In nature, BbCRASP-1 exists as a homodimer bound to the spirochete's surface <ref name="Cordes">PMID: 15711564</ref>. Researchers confirmed this by viewing the presence of pieces of the dimer in solution <ref name="Cordes">PMID: 15711564</ref>. They viewed the results through analytical ultracentrifugation and saw that dimeric crystals formed. If its dimeric state is threatened, BbCRASP-1 would not be able to function.

=== '''Importance of the C-terminus''' ===

Sequences of high conservation in the C-terminal regions of the protein’s monomers, <scene name='SB2013_L01gr6/C-terminus/1'>residues 241 to 250</scene> , were of interest as a potential binding site <ref name="Cordes">PMID: 15711564</ref>. Previous studies showed that deletion of these sites caused a complete inability of BbCRASP-1 to bind FH and FHL-1 regulators (Kraiczy P et al. 2004). Scientists determined whether the role of the C-terminus region was in maintaining structure or directly functioning as a binding site by mutating <scene name='SB2013_L01gr6/Leucine_246/1'>leucine 246</scene> in the C-terminus region of the dimer to aspartate <ref name="Cordes">PMID: 15711564</ref>. This new polar molecule disrupted the hydrophobic interactions in the core of the C-terminal region and caused the entire structure to aggregate as functionally inert mutants. Both the C-terminally truncated and mutated BbCRASP-1 proteins lost their ability to dimerize, inhibiting them from binding to their host’s regulatory factors. It was then concluded that the C-terminus is a structurally sensitive region rather than a direct binding site <ref name="Cordes">PMID: 15711564</ref>. The C-terminus aids in the stabilization of the dimer by holding the <scene name='SB2013_L01gr6/Monomers/1'>two monomers</scene> in place. The C-terminal of one monomer lies against the <scene name='SB2013_L01gr6/N-terminal_helix/1'>N-terminal half of the helix</scene> of the other and keeps the structure together <ref name="Cordes">PMID: 15711564</ref>.

=== '''Other Potential Binding Sites''' ===

Additional studies were done to investigate the FH and FHL-1 binding sites on the protein. As with previous research, areas of high conservation were investigated due to their relationship with upholding the structure and function of the protein (Cordes et al. 2010). Researchers examined highly conserved areas of amino acid sequences along the <scene name='SB2013_L01gr6/Pocket_region/1'>cleft region</scene> of the protein. They saw that the majority of these regions clustered on a highly-exposed region of the protein.

=== References ===

<references />

Complement Regulator-Acquiring Surface Protein

2013-05-05T01:53:45Z

Dipanshu Walia:

<Structure load='1w33' size='250' frame='true' align='right' caption='BbCRASP-1' scene='Insert optional scene name here' />

== '''Introduction''' ==

Lyme disease is caused by the spirochete ''Borrelia burgdorferi'', and is transferred into vertebrate hosts by zoonotic vectors such as ''Ixodes'' ticks <ref name="Bykowski">PMID: 17562769</ref>. There are thousands of cases of Lyme disease reported each year, making it a prevalent disease in North America and Eurasia <ref name="Cordes">PMID: 15711564</ref>. In order for ''B. burgdorferi'' to survive in its host, it evades the host's immune system through the use of complement regulator-acquiring surface proteins. One such protein responsible for a successful initial infection is ''Borrelia burgdorferi'' complement regulator-acquiring surface protein 1, or BbCRASP-1 (Bykowski et al. 2007). Because BbCRASP-1 binds host complement regulators to the spirochete's outer surface, ''B. burgdorferi'' remains undetected within the host (Bykowski et al. 2007). BbCRASP-1 specifically binds to complement Factor H (FH) and Factor H-like proteins (FHL-1), which are responsible for the host's immune response and detection of pathogens (Kraiczy et al. 2004). Recently, it was found that BbCRASP-1 binds to several other proteins in the extra cellular matrix of a human cell.

== '''Function''' ==

BbCRASP-1 can be found on the outer layer of the Lyme disease spirochete and is essential for the infiltration of the spirochete into the host (Bykowski 2007). BbCRASP-1 provides resistance for the spirochete against the host's complementary immune system as well as spreading of the spirochete within the host.

=== '''Host Immune Response Evasion''' ===

BbCRASP-1 has an affinity for Factor H and Factor H-like proteins. Therefore, Factor H binds to BbCRASP-1, which is bound to the outer surface of the spirochete. Because there are multiple BbCRASP-1 proteins on the spirochete, the spirochete is coated with [http://www.uniprot.org/uniprot/CFAH_HUMAN Factor H] and effectively able to infiltrate the host and go undetected in the host's plasma(Bykowski 2007).

=== '''Relation to the Extra Cellular Matrix''' ===

Recently it was found that BbCRASP-1 not only binds to FH and FHL-1 proteins, but it also binds to several other human ligands such as [http://www.uniprot.org/uniprot/BMP2_HUMAN BMP-2] and Extra cellular matrix ligands Collagen I, Collagen III, Collagen IV, fibronectin, laminin, and plasminogen (Hallstrom et al. 2010). As a result of this new finding, BbCRASP-1 is said to advocate the bypassing of the complementary immune system in addition to the pathogenesis of Lyme disease. BbCRASP-1 facilitates binding of “Borrelia burgdoferi” to human cells and tissues, which helps spread the infection (Hallstrom et al. 2010).

<applet load='BBCRASP-12' size='250' frame='true' align='right' caption='BbCRASP-1' scene='Insert optional scene name here' />

== '''Structure''' ==

In nature, BbCRASP-1 exists as a homodimer bound to the spirochete's surface <ref name="Cordes">PMID: 15711564</ref>. Researchers confirmed this by viewing the presence of pieces of the dimer in solution <ref name="Cordes">PMID: 15711564</ref>. They viewed the results through analytical ultracentrifugation and saw that dimeric crystals formed. If its dimeric state is threatened, BbCRASP-1 would not be able to function.

=== '''Importance of the C-terminus''' ===

Sequences of high conservation in the C-terminal regions of the protein’s monomers, <scene name='SB2013_L01gr6/C-terminus/1'>residues 241 to 250</scene> , were of interest as a potential binding site <ref name="Cordes">PMID: 15711564</ref>. Previous studies showed that deletion of these sites caused a complete inability of BbCRASP-1 to bind FH and FHL-1 regulators (Kraiczy P et al. 2004). Scientists determined whether the role of the C-terminus region was in maintaining structure or directly functioning as a binding site by mutating <scene name='SB2013_L01gr6/Leucine_246/1'>leucine 246</scene> in the C-terminus region of the dimer to aspartate <ref name="Cordes">PMID: 15711564</ref>. This new polar molecule disrupted the hydrophobic interactions in the core of the C-terminal region and caused the entire structure to aggregate as functionally inert mutants. Both the C-terminally truncated and mutated BbCRASP-1 proteins lost their ability to dimerize, inhibiting them from binding to their host’s regulatory factors. It was then concluded that the C-terminus is a structurally sensitive region rather than a direct binding site <ref name="Cordes">PMID: 15711564</ref>. The C-terminus aids in the stabilization of the dimer by holding the <scene name='SB2013_L01gr6/Monomers/1'>two monomers</scene> in place. The C-terminal of one monomer lies against the <scene name='SB2013_L01gr6/N-terminal_helix/1'>N-terminal half of the helix</scene> of the other and keeps the structure together <ref name="Cordes">PMID: 15711564</ref>.

=== '''Other Potential Binding Sites''' ===

Additional studies were done to investigate the FH and FHL-1 binding sites on the protein. As with previous research, areas of high conservation were investigated due to their relationship with upholding the structure and function of the protein (Cordes et al. 2010). Researchers examined highly conserved areas of amino acid sequences along the <scene name='SB2013_L01gr6/Pocket_region/1'>cleft region</scene> of the protein. They saw that the majority of these regions clustered on a highly-exposed region of the protein.

=== References ===

<references />

Complement Regulator-Acquiring Surface Protein

2013-05-05T01:52:10Z

Dipanshu Walia:

<Structure load='1w33' size='250' frame='true' align='right' caption='BbCRASP-1' scene='Insert optional scene name here' />

== '''Introduction''' ==

Lyme disease is caused by the spirochete ''Borrelia burgdorferi'', and is transferred into vertebrate hosts by zoonotic vectors such as ''Ixodes'' ticks (Bykowski et al. 2007). There are thousands of cases of Lyme disease reported each year, making it a prevalent disease in North America and Eurasia <ref name="Cordes">PMID: 15711564</ref>. In order for ''B. burgdorferi'' to survive in its host, it evades the host's immune system through the use of complement regulator-acquiring surface proteins. One such protein responsible for a successful initial infection is ''Borrelia burgdorferi'' complement regulator-acquiring surface protein 1, or BbCRASP-1 (Bykowski et al. 2007). Because BbCRASP-1 binds host complement regulators to the spirochete's outer surface, ''B. burgdorferi'' remains undetected within the host (Bykowski et al. 2007). BbCRASP-1 specifically binds to complement Factor H (FH) and Factor H-like proteins (FHL-1), which are responsible for the host's immune response and detection of pathogens (Kraiczy et al. 2004). Recently, it was found that BbCRASP-1 binds to several other proteins in the extra cellular matrix of a human cell.

== '''Function''' ==

BbCRASP-1 can be found on the outer layer of the Lyme disease spirochete and is essential for the infiltration of the spirochete into the host (Bykowski 2007). BbCRASP-1 provides resistance for the spirochete against the host's complementary immune system as well as spreading of the spirochete within the host.

=== '''Host Immune Response Evasion''' ===

BbCRASP-1 has an affinity for Factor H and Factor H-like proteins. Therefore, Factor H binds to BbCRASP-1, which is bound to the outer surface of the spirochete. Because there are multiple BbCRASP-1 proteins on the spirochete, the spirochete is coated with [http://www.uniprot.org/uniprot/CFAH_HUMAN Factor H] and effectively able to infiltrate the host and go undetected in the host's plasma(Bykowski 2007).

=== '''Relation to the Extra Cellular Matrix''' ===

Recently it was found that BbCRASP-1 not only binds to FH and FHL-1 proteins, but it also binds to several other human ligands such as [http://www.uniprot.org/uniprot/BMP2_HUMAN BMP-2] and Extra cellular matrix ligands Collagen I, Collagen III, Collagen IV, fibronectin, laminin, and plasminogen (Hallstrom et al. 2010). As a result of this new finding, BbCRASP-1 is said to advocate the bypassing of the complementary immune system in addition to the pathogenesis of Lyme disease. BbCRASP-1 facilitates binding of “Borrelia burgdoferi” to human cells and tissues, which helps spread the infection (Hallstrom et al. 2010).

<applet load='BBCRASP-12' size='250' frame='true' align='right' caption='BbCRASP-1' scene='Insert optional scene name here' />

== '''Structure''' ==

In nature, BbCRASP-1 exists as a homodimer bound to the spirochete's surface <ref name="Cordes">PMID: 15711564</ref>. Researchers confirmed this by viewing the presence of pieces of the dimer in solution <ref name="Cordes">PMID: 15711564</ref>. They viewed the results through analytical ultracentrifugation and saw that dimeric crystals formed. If its dimeric state is threatened, BbCRASP-1 would not be able to function.

=== '''Importance of the C-terminus''' ===

Sequences of high conservation in the C-terminal regions of the protein’s monomers, <scene name='SB2013_L01gr6/C-terminus/1'>residues 241 to 250</scene> , were of interest as a potential binding site <ref name="Cordes">PMID: 15711564</ref>. Previous studies showed that deletion of these sites caused a complete inability of BbCRASP-1 to bind FH and FHL-1 regulators (Kraiczy P et al. 2004). Scientists determined whether the role of the C-terminus region was in maintaining structure or directly functioning as a binding site by mutating <scene name='SB2013_L01gr6/Leucine_246/1'>leucine 246</scene> in the C-terminus region of the dimer to aspartate <ref name="Cordes">PMID: 15711564</ref>. This new polar molecule disrupted the hydrophobic interactions in the core of the C-terminal region and caused the entire structure to aggregate as functionally inert mutants. Both the C-terminally truncated and mutated BbCRASP-1 proteins lost their ability to dimerize, inhibiting them from binding to their host’s regulatory factors. It was then concluded that the C-terminus is a structurally sensitive region rather than a direct binding site <ref name="Cordes">PMID: 15711564</ref>. The C-terminus aids in the stabilization of the dimer by holding the <scene name='SB2013_L01gr6/Monomers/1'>two monomers</scene> in place. The C-terminal of one monomer lies against the <scene name='SB2013_L01gr6/N-terminal_helix/1'>N-terminal half of the helix</scene> of the other and keeps the structure together <ref name="Cordes">PMID: 15711564</ref>.

=== '''Other Potential Binding Sites''' ===

Additional studies were done to investigate the FH and FHL-1 binding sites on the protein. As with previous research, areas of high conservation were investigated due to their relationship with upholding the structure and function of the protein (Cordes et al. 2010). Researchers examined highly conserved areas of amino acid sequences along the <scene name='SB2013_L01gr6/Pocket_region/1'>cleft region</scene> of the protein. They saw that the majority of these regions clustered on a highly-exposed region of the protein.

=== References ===

<references />

Complement Regulator-Acquiring Surface Protein

2013-05-05T01:50:09Z

Dipanshu Walia:

<Structure load='1w33' size='250' frame='true' align='right' caption='BbCRASP-1' scene='Insert optional scene name here' />

== '''Introduction''' ==

Lyme disease is caused by the spirochete ''Borrelia burgdorferi'', and is transferred into vertebrate hosts by zoonotic vectors such as ''Ixodes'' ticks (Bykowski et al. 2007). There are thousands of cases of Lyme disease reported each year, making it a prevalent disease in North America and Eurasia <ref name="Cordes">PMID: 15711564</ref>. In order for ''B. burgdorferi'' to survive in its host, it evades the host's immune system through the use of complement regulator-acquiring surface proteins. One such protein responsible for a successful initial infection is ''Borrelia burgdorferi'' complement regulator-acquiring surface protein 1, or BbCRASP-1 (Bykowski et al. 2007). Because BbCRASP-1 binds host complement regulators to the spirochete's outer surface, ''B. burgdorferi'' remains undetected within the host (Bykowski et al. 2007). BbCRASP-1 specifically binds to complement Factor H (FH) and Factor H-like proteins (FHL-1), which are responsible for the host's immune response and detection of pathogens (Kraiczy et al. 2004). Recently, it was found that BbCRASP-1 binds to several other proteins in the extra cellular matrix of a human cell.

== '''Function''' ==

BbCRASP-1 can be found on the outer layer of the Lyme disease spirochete and is essential for the infiltration of the spirochete into the host (Bykowski 2007). BbCRASP-1 provides resistance for the spirochete against the host's complementary immune system as well as spreading of the spirochete within the host.

=== '''Host Immune Response Evasion''' ===

BbCRASP-1 has an affinity for Factor H and Factor H-like proteins. Therefore, Factor H binds to BbCRASP-1, which is bound to the outer surface of the spirochete. Because there are multiple BbCRASP-1 proteins on the spirochete, the spirochete is coated with [http://www.uniprot.org/uniprot/CFAH_HUMAN Factor H] and effectively able to infiltrate the host and go undetected in the host's plasma(Bykowski 2007).

=== '''Relation to the Extra Cellular Matrix''' ===

Recently it was found that BbCRASP-1 not only binds to FH and FHL-1 proteins, but it also binds to several other human ligands such as [http://www.uniprot.org/uniprot/BMP2_HUMAN BMP-2] and Extra cellular matrix ligands Collagen I, Collagen III, Collagen IV, fibronectin, laminin, and plasminogen (Hallstrom et al. 2010). As a result of this new finding, BbCRASP-1 is said to advocate the bypassing of the complementary immune system in addition to the pathogenesis of Lyme disease. BbCRASP-1 facilitates binding of “Borrelia burgdoferi” to human cells and tissues, which helps spread the infection (Hallstrom et al. 2010).

<applet load='BBCRASP-12' size='250' frame='true' align='right' caption='BbCRASP-1' scene='Insert optional scene name here' />

== '''Structure''' ==

In nature, BbCRASP-1 exists as a homodimer bound to the spirochete's surface (Cordes et al. 2005). Researchers confirmed this by viewing the presence of pieces of the dimer in solution (Cordes et al. 2005). They viewed the results through analytical ultracentrifugation and saw that dimeric crystals formed. If its dimeric state is threatened, BbCRASP-1 would not be able to function.

=== '''Importance of the C-terminus''' ===

Sequences of high conservation in the C-terminal regions of the protein’s monomers, <scene name='SB2013_L01gr6/C-terminus/1'>residues 241 to 250</scene> , were of interest as a potential binding site (Cordes F et al. 2005). Previous studies showed that deletion of these sites caused a complete inability of BbCRASP-1 to bind FH and FHL-1 regulators (Kraiczy P et al. 2004). Scientists determined whether the role of the C-terminus region was in maintaining structure or directly functioning as a binding site by mutating <scene name='SB2013_L01gr6/Leucine_246/1'>leucine 246</scene> in the C-terminus region of the dimer to aspartate (Cordes F et al. 2005). This new polar molecule disrupted the hydrophobic interactions in the core of the C-terminal region and caused the entire structure to aggregate as functionally inert mutants. Both the C-terminally truncated and mutated BbCRASP-1 proteins lost their ability to dimerize, inhibiting them from binding to their host’s regulatory factors. It was then concluded that the C-terminus is a structurally sensitive region rather than a direct binding site (Cordes 2005). The C-terminus aids in the stabilization of the dimer by holding the <scene name='SB2013_L01gr6/Monomers/1'>two monomers</scene> in place. The C-terminal of one monomer lies against the <scene name='SB2013_L01gr6/N-terminal_helix/1'>N-terminal half of the helix</scene> of the other and keeps the structure together (Cordes F et al. 2005).

=== '''Other Potential Binding Sites''' ===

Additional studies were done to investigate the FH and FHL-1 binding sites on the protein. As with previous research, areas of high conservation were investigated due to their relationship with upholding the structure and function of the protein (Cordes et al. 2010). Researchers examined highly conserved areas of amino acid sequences along the <scene name='SB2013_L01gr6/Pocket_region/1'>cleft region</scene> of the protein. They saw that the majority of these regions clustered on a highly-exposed region of the protein.

=== References ===

<references />

Complement Regulator-Acquiring Surface Protein

2013-05-05T01:48:42Z

Dipanshu Walia:

<Structure load='1w33' size='250' frame='true' align='right' caption='BbCRASP-1' scene='Insert optional scene name here' />

== '''Introduction''' ==

Lyme disease is caused by the spirochete ''Borrelia burgdorferi'', and is transferred into vertebrate hosts by zoonotic vectors such as ''Ixodes'' ticks (Bykowski et al. 2007). There are thousands of cases of Lyme disease reported each year, making it a prevalent disease in North America and Eurasia (Cordes et al. 2005). In order for ''B. burgdorferi'' to survive in its host, it evades the host's immune system through the use of complement regulator-acquiring surface proteins. One such protein responsible for a successful initial infection is ''Borrelia burgdorferi'' complement regulator-acquiring surface protein 1, or BbCRASP-1 (Bykowski et al. 2007). Because BbCRASP-1 binds host complement regulators to the spirochete's outer surface, ''B. burgdorferi'' remains undetected within the host (Bykowski et al. 2007). BbCRASP-1 specifically binds to complement Factor H (FH) and Factor H-like proteins (FHL-1), which are responsible for the host's immune response and detection of pathogens (Kraiczy et al. 2004). Recently, it was found that BbCRASP-1 binds to several other proteins in the extra cellular matrix of a human cell.

== '''Function''' ==

BbCRASP-1 can be found on the outer layer of the Lyme disease spirochete and is essential for the infiltration of the spirochete into the host (Bykowski 2007). BbCRASP-1 provides resistance for the spirochete against the host's complementary immune system as well as spreading of the spirochete within the host.

=== '''Host Immune Response Evasion''' ===

BbCRASP-1 has an affinity for Factor H and Factor H-like proteins. Therefore, Factor H binds to BbCRASP-1, which is bound to the outer surface of the spirochete. Because there are multiple BbCRASP-1 proteins on the spirochete, the spirochete is coated with [http://www.uniprot.org/uniprot/CFAH_HUMAN Factor H] and effectively able to infiltrate the host and go undetected in the host's plasma(Bykowski 2007).

=== '''Relation to the Extra Cellular Matrix''' ===

Recently it was found that BbCRASP-1 not only binds to FH and FHL-1 proteins, but it also binds to several other human ligands such as [http://www.uniprot.org/uniprot/BMP2_HUMAN BMP-2] and Extra cellular matrix ligands Collagen I, Collagen III, Collagen IV, fibronectin, laminin, and plasminogen (Hallstrom et al. 2010). As a result of this new finding, BbCRASP-1 is said to advocate the bypassing of the complementary immune system in addition to the pathogenesis of Lyme disease. BbCRASP-1 facilitates binding of “Borrelia burgdoferi” to human cells and tissues, which helps spread the infection (Hallstrom et al. 2010).

<applet load='BBCRASP-12' size='250' frame='true' align='right' caption='BbCRASP-1' scene='Insert optional scene name here' />

== '''Structure''' ==

In nature, BbCRASP-1 exists as a homodimer bound to the spirochete's surface (Cordes et al. 2005). Researchers confirmed this by viewing the presence of pieces of the dimer in solution (Cordes et al. 2005). They viewed the results through analytical ultracentrifugation and saw that dimeric crystals formed. If its dimeric state is threatened, BbCRASP-1 would not be able to function.

=== '''Importance of the C-terminus''' ===

Sequences of high conservation in the C-terminal regions of the protein’s monomers, <scene name='SB2013_L01gr6/C-terminus/1'>residues 241 to 250</scene> , were of interest as a potential binding site (Cordes F et al. 2005). Previous studies showed that deletion of these sites caused a complete inability of BbCRASP-1 to bind FH and FHL-1 regulators (Kraiczy P et al. 2004). Scientists determined whether the role of the C-terminus region was in maintaining structure or directly functioning as a binding site by mutating <scene name='SB2013_L01gr6/Leucine_246/1'>leucine 246</scene> in the C-terminus region of the dimer to aspartate (Cordes F et al. 2005). This new polar molecule disrupted the hydrophobic interactions in the core of the C-terminal region and caused the entire structure to aggregate as functionally inert mutants. Both the C-terminally truncated and mutated BbCRASP-1 proteins lost their ability to dimerize, inhibiting them from binding to their host’s regulatory factors. It was then concluded that the C-terminus is a structurally sensitive region rather than a direct binding site (Cordes 2005). The C-terminus aids in the stabilization of the dimer by holding the <scene name='SB2013_L01gr6/Monomers/1'>two monomers</scene> in place. The C-terminal of one monomer lies against the <scene name='SB2013_L01gr6/N-terminal_helix/1'>N-terminal half of the helix</scene> of the other and keeps the structure together (Cordes F et al. 2005).

=== '''Other Potential Binding Sites''' ===

Additional studies were done to investigate the FH and FHL-1 binding sites on the protein. As with previous research, areas of high conservation were investigated due to their relationship with upholding the structure and function of the protein (Cordes et al. 2010). Researchers examined highly conserved areas of amino acid sequences along the <scene name='SB2013_L01gr6/Pocket_region/1'>cleft region</scene> of the protein. They saw that the majority of these regions clustered on a highly-exposed region of the protein.

=== References ===

<references />

Complement Regulator-Acquiring Surface Protein

2013-05-05T01:36:08Z

Dipanshu Walia:

<Structure load='1w33' size='250' frame='true' align='right' caption='BbCRASP-1' scene='Insert optional scene name here' />

== '''Introduction''' ==

Lyme disease is caused by the spirochete ''Borrelia burgdorferi'', and is transferred into vertebrate hosts by zoonotic vectors such as ''Ixodes'' ticks (Bykowski et al. 2007). There are thousands of cases of Lyme disease reported each year, making it a prevalent disease in North America and Eurasia (Cordes et al. 2005). In order for ''B. burgdorferi'' to survive in its host, it evades the host's immune system through the use of complement regulator-acquiring surface proteins. One such protein responsible for a successful initial infection is ''Borrelia burgdorferi'' complement regulator-acquiring surface protein 1, or BbCRASP-1 (Bykowski et al. 2007). Because BbCRASP-1 binds host complement regulators to the spirochete's outer surface, ''B. burgdorferi'' remains undetected within the host (Bykowski et al. 2007). BbCRASP-1 specifically binds to complement Factor H (FH) and Factor H-like proteins (FHL-1), which are responsible for the host's immune response and detection of pathogens (Kraiczy et al. 2004). Recently, it was found that BbCRASP-1 binds to several other proteins in the extra cellular matrix of a human cell.

== '''Function''' ==

BbCRASP-1 can be found on the outer layer of the Lyme disease spirochete and is essential for the infiltration of the spirochete into the host (Bykowski 2007). BbCRASP-1 provides resistance for the spirochete against the host's complementary immune system as well as spreading of the spirochete within the host.

=== '''Host Immune Response Evasion''' ===

BbCRASP-1 has an affinity for Factor H and Factor H-like proteins. Therefore, Factor H binds to BbCRASP-1, which is bound to the outer surface of the spirochete. Because there are multiple BbCRASP-1 proteins on the spirochete, the spirochete is coated with [http://www.uniprot.org/uniprot/CFAH_HUMAN Factor H] and effectively able to infiltrate the host and go undetected in the host's plasma(Bykowski 2007).

=== '''Relation to the Extra Cellular Matrix''' ===

Recently it was found that BbCRASP-1 not only binds to FH and FHL-1 proteins, but it also binds to several other human ligands such as [http://www.uniprot.org/uniprot/BMP2_HUMAN BMP-2] and Extra cellular matrix ligands Collagen I, Collagen III, Collagen IV, fibronectin, laminin, and plasminogen (Hallstrom et al. 2010). As a result of this new finding, BbCRASP-1 is said to advocate the bypassing of the complementary immune system in addition to the pathogenesis of Lyme disease. BbCRASP-1 facilitates binding of “Borrelia burgdoferi” to human cells and tissues, which helps spread the infection (Hallstrom et al. 2010).

<applet load='BBCRASP-12' size='250' frame='true' align='right' caption='BbCRASP-1' scene='Insert optional scene name here' />

== '''Structure''' ==

In nature, BbCRASP-1 exists as a homodimer bound to the spirochete's surface (Cordes et al. 2005). Researchers confirmed this by viewing the presence of pieces of the dimer in solution (Cordes et al. 2005). They viewed the results through analytical ultracentrifugation and saw that dimeric crystals formed. If its dimeric state is threatened, BbCRASP-1 would not be able to function.

=== '''Importance of the C-terminus''' ===

Sequences of high conservation in the C-terminal regions of the protein’s monomers, <scene name='SB2013_L01gr6/C-terminus/1'>residues 241 to 250</scene> , were of interest as a potential binding site (Cordes F et al. 2005). Previous studies showed that deletion of these sites caused a complete inability of BbCRASP-1 to bind FH and FHL-1 regulators (Kraiczy P et al. 2004). Scientists determined whether the role of the C-terminus region was in maintaining structure or directly functioning as a binding site by mutating <scene name='SB2013_L01gr6/Leucine_246/1'>leucine 246</scene> in the C-terminus region of the dimer to aspartate (Cordes F et al. 2005). This new polar molecule disrupted the hydrophobic interactions in the core of the C-terminal region and caused the entire structure to aggregate as functionally inert mutants. Both the C-terminally truncated and mutated BbCRASP-1 proteins lost their ability to dimerize, inhibiting them from binding to their host’s regulatory factors. It was then concluded that the C-terminus is a structurally sensitive region rather than a direct binding site (Cordes 2005). The C-terminus aids in the stabilization of the dimer by holding the <scene name='SB2013_L01gr6/Monomers/1'>two monomers</scene> in place. The C-terminal of one monomer lies against the <scene name='SB2013_L01gr6/N-terminal_helix/1'>N-terminal half of the helix</scene> of the other and keeps the structure together (Cordes F et al. 2005).

=== '''Other Potential Binding Sites''' ===

Additional studies were done to investigate the FH and FHL-1 binding sites on the protein. As with previous research, areas of high conservation were investigated due to their relationship with upholding the structure and function of the protein (Cordes et al. 2010). Researchers examined highly conserved areas of amino acid sequences along the <scene name='SB2013_L01gr6/Pocket_region/1'>cleft region</scene> of the protein. They saw that the majority of these regions clustered on a highly-exposed region of the protein.

Complement Regulator-Acquiring Surface Protein

2013-05-05T01:33:07Z

Dipanshu Walia:

<Structure load='1w33' size='250' frame='true' align='right' caption='BbCRASP-1' scene='Insert optional scene name here' />

== '''Introduction''' ==

Lyme disease is caused by the spirochete ''Borrelia burgdorferi'', and is transferred into vertebrate hosts by zoonotic vectors such as ''Ixodes'' ticks (Bykowski et al. 2007). There are thousands of cases of Lyme disease reported each year, making it a prevalent disease in North America and Eurasia (Cordes et al. 2005). In order for ''B. burgdorferi'' to survive in its host, it evades the host's immune system through the use of complement regulator-acquiring surface proteins. One such protein responsible for a successful initial infection is ''Borrelia burgdorferi'' complement regulator-acquiring surface protein 1, or BbCRASP-1 (Bykowski et al. 2007). Because BbCRASP-1 binds host complement regulators to the spirochete's outer surface, ''B. burgdorferi'' remains undetected within the host (Bykowski et al. 2007). BbCRASP-1 specifically binds to complement Factor H (FH) and Factor H-like proteins (FHL-1), which are responsible for the host's immune response and detection of pathogens (Kraiczy et al. 2004). Recently, it was found that BbCRASP-1 binds to several other proteins in the extra cellular matrix of a human cell.

== '''Function''' ==

BbCRASP-1 can be found on the outer layer of the Lyme disease spirochete and is essential for the infiltration of the spirochete into the host (Bykowski 2007). BbCRASP-1 provides resistance for the spirochete against the host's complementary immune system as well as spreading of the spirochete within the host.

=== '''Host Immune Response Evasion''' ===

BbCRASP-1 has an affinity for Factor H and Factor H-like proteins. Therefore, Factor H binds to BbCRASP-1, which is bound to the outer surface of the spirochete. Because there are multiple BbCRASP-1 proteins on the spirochete, the spirochete is coated with [http://www.uniprot.org/uniprot/CFAH_HUMAN Factor H] and effectively able to infiltrate the host and go undetected in the host's plasma(Bykowski 2007).

=== '''Relation to the Extra Cellular Matrix''' ===

Recently it was found that BbCRASP-1 not only binds to FH and FHL-1 proteins, but it also binds to several other human ligands such as [http://www.uniprot.org/uniprot/BMP2_HUMAN BMP-2] and Extra cellular matrix ligands Collagen I, Collagen III, Collagen IV, fibronectin, laminin, and plasminogen (Hallstrom et al. 2010). As a result of this new finding, BbCRASP-1 is said to advocate the bypassing of the complementary immune system in addition to the pathogenesis of Lyme disease. BbCRASP-1 facilitates binding of “Borrelia burgdoferi” to human cells and tissues, which helps spread the infection (Hallstrom et al. 2010).

<applet load='BBCRASP-12' size='250' frame='true' align='right' caption='BbCRASP-1' scene='Insert optional scene name here' />

== '''Structure''' ==

In nature, BbCRASP-1 exists as a homodimer bound to the spirochete's surface (Cordes et al. 2005). Researchers confirmed this by viewing the presence of pieces of the dimer in solution (Cordes et al. 2005). They viewed the results through analytical ultracentrifugation and saw that dimeric crystals formed. If its dimeric state is threatened, BbCRASP-1 would not be able to function.

=== '''Importance of the C-terminus''' ===

Sequences of high conservation in the C-terminal regions of the protein’s monomers, <scene name='SB2013_L01gr6/C-terminus/1'>residues 241 to 250</scene> , were of interest as a potential binding site (Cordes F et al. 2005). Previous studies showed that deletion of these sites caused a complete inability of BbCRASP-1 to bind FH and FHL-1 regulators (Kraiczy P et al. 2004). Scientists determined whether the role of the C-terminus region was in maintaining structure or directly functioning as a binding site by mutating <scene name='SB2013_L01gr6/Leucine_246/1'>leucine 246</scene> in the C-terminus region of the dimer to aspartate (Cordes F et al. 2005). This new polar molecule disrupted the hydrophobic interactions in the core of the C-terminal region and caused the entire structure to aggregate as functionally inert mutants. Both the C-terminally truncated and mutated BbCRASP-1 proteins lost their ability to dimerize, inhibiting them from binding to their host’s regulatory factors. It was then concluded that the C-terminus is a structurally sensitive region rather than a direct binding site (Cordes 2005). The C-terminus aids in the stabilization of the dimer by holding the <scene name='SB2013_L01gr6/Monomers/1'>two monomers</scene> in place. The C-terminal of one monomer lies against the <scene name='SB2013_L01gr6/N-terminal_helix/1'>N-terminal half of the helix</scene> of the other and keeps the structure together (Cordes F et al. 2005).

=== '''Other Potential Binding Sites''' ===

Additional studies were done to investigate the FH and FHL-1 binding sites on the protein. As with previous research, areas of high conservation were investigated due to their relationship with upholding the structure and function of the protein (Cordes et al. 2010). Researchers examined highly conserved areas of amino acid sequences along the <scene name='SB2013_L01gr6/Pocket_region/1'>cleft region</scene> of the protein.

Complement Regulator-Acquiring Surface Protein

2013-05-05T01:10:01Z

Dipanshu Walia:

<Structure load='1w33' size='250' frame='true' align='right' caption='BbCRASP-1' scene='Insert optional scene name here' />

== '''Introduction''' ==

Lyme disease is caused by the spirochete ''Borrelia burgdorferi'', and is transferred into vertebrate hosts by zoonotic vectors such as ''Ixodes'' ticks (Bykowski et al. 2007). There are thousands of cases of Lyme disease reported each year, making it a prevalent disease in North America and Eurasia (Cordes et al. 2005). In order for ''B. burgdorferi'' to survive in its host, it evades the host's immune system through the use of complement regulator-acquiring surface proteins. One such protein responsible for a successful initial infection is ''Borrelia burgdorferi'' complement regulator-acquiring surface protein 1, or BbCRASP-1 (Bykowski et al. 2007). Because BbCRASP-1 binds host complement regulators to the spirochete's outer surface, ''B. burgdorferi'' remains undetected within the host (Bykowski et al. 2007). BbCRASP-1 specifically binds to complement Factor H (FH) and Factor H-like proteins (FHL-1), which are responsible for the host's immune response and detection of pathogens (Kraiczy et al. 2004). Recently, it was found that BbCRASP-1 binds to several other proteins in the extra cellular matrix of a human cell.

== '''Function''' ==

BbCRASP-1 can be found on the outer layer of the Lyme disease spirochete and is essential for the infiltration of the spirochete into the host (Bykowski 2007). BbCRASP-1 provides resistance for the spirochete against the host's complementary immune system as well as spreading of the spirochete within the host.

=== '''Host Immune Response Evasion''' ===

BbCRASP-1 has an affinity for Factor H and Factor H-like proteins. Therefore, Factor H binds to BbCRASP-1, which is bound to the outer surface of the spirochete. Because there are multiple BbCRASP-1 proteins on the spirochete, the spirochete is coated with [http://www.uniprot.org/uniprot/CFAH_HUMAN Factor H] and effectively able to infiltrate the host and go undetected in the host's plasma(Bykowski 2007).

=== '''Relation to the Extra Cellular Matrix''' ===

Recently it was found that BbCRASP-1 not only binds to FH and FHL-1 proteins, but it also binds to several other human ligands such as [http://www.uniprot.org/uniprot/BMP2_HUMAN BMP-2] and Extra cellular matrix ligands Collagen I, Collagen III, Collagen IV, fibronectin, laminin, and plasminogen (Hallstrom et al. 2010). As a result of this new finding, BbCRASP-1 is said to advocate the bypassing of the complementary immune system in addition to the pathogenesis of Lyme disease. BbCRASP-1 facilitates binding of “Borrelia burgdoferi” to human cells and tissues, which helps spread the infection (Hallstrom et al. 2010).

<applet load='BBCRASP-12' size='250' frame='true' align='right' caption='BbCRASP-1' scene='Insert optional scene name here' />

== '''Structure''' ==

In nature, BbCRASP-1 exists as a homodimer bound to the spirochete's surface. Various studies were done to investigate the FH and FHL-1 binding sites on the protein. Sequences of high conservation in the C-terminal regions of the protein’s monomers, <scene name='SB2013_L01gr6/C-terminus/1'>residues 241 to 250</scene> , were of interest as a potential binding site (Cordes F et al. 2005). Previous studies showed that deletion of these sites caused a complete inability of BbCRASP-1 to bind FH and FHL-1 regulators (Kraiczy P et al. 2004). Scientists determined whether the role of the C-terminus region was in maintaining structure or directly functioning as a binding site by mutating <scene name='SB2013_L01gr6/Leucine_246/1'>leucine 246</scene> in the C-terminus region of the dimer to aspartate (Cordes F et al. 2005). This new polar molecule disrupted the hydrophobic interactions in the core of the C-terminal region and caused the entire structure to aggregate as functionally inert mutants. Both the C-terminally truncated and mutated BbCRASP-1 proteins lost their ability to dimerize, inhibiting them from binding to their host’s regulatory factors. It was then concluded that the C-terminus is a structurally sensitive region rather than a direct binding site (Cordes 2005). The C-terminus aids in the stabilization of the dimer by holding the <scene name='SB2013_L01gr6/Monomers/1'>two monomers</scene> in place. The C-terminal of one monomer lies against the <scene name='SB2013_L01gr6/N-terminal_helix/1'>N-terminal half of the helix</scene> of the other and keeps the structure together (Cordes F et al. 2005).

In nature, BbCRASP-1 exists as a dimer. Researchers confirmed this by viewing the presence of pieces of the dimer in solution (Cordes et al. 2005). They viewed the results through analytical ultracentrifugation and saw that dimeric crystals formed. If its dimeric state is threatened, BbCRASP-1 would not be able to function.

Complement Regulator-Acquiring Surface Protein

2013-05-05T01:05:37Z

Dipanshu Walia:

<Structure load='1w33' size='250' frame='true' align='right' caption='BbCRASP-1' scene='Insert optional scene name here' />

== '''Introduction''' ==

Lyme disease is caused by the spirochete ''Borrelia burgdorferi'', and is transferred into vertebrate hosts by zoonotic vectors such as ''Ixodes'' ticks (Bykowski et al. 2007). There are thousands of cases of Lyme disease reported each year, making it a prevalent disease in North America and Eurasia (Cordes et al. 2005). In order for ''B. burgdorferi'' to survive in its host, it evades the host's immune system through the use of complement regulator-acquiring surface proteins. One such protein responsible for a successful initial infection is ''Borrelia burgdorferi'' complement regulator-acquiring surface protein 1, or BbCRASP-1 (Bykowski et al. 2007). Because BbCRASP-1 binds host complement regulators to the spirochete's outer surface, ''B. burgdorferi'' remains undetected within the host (Bykowski et al. 2007). BbCRASP-1 specifically binds to complement Factor H (FH) and Factor H-like proteins (FHL-1), which are responsible for the host's immune response and detection of pathogens (Kraiczy et al. 2004). Recently, it was found that BbCRASP-1 binds to several other proteins in the extra cellular matrix of a human cell.

== '''Function''' ==

Bb CRASP-1 can be found on the outer layer of the Lyme disease spirochete and is essential for the infiltration of the spirochete into the host (Bykowski 2007). BbCRASP-1 provides resistance for the spirochete against the host's complementary immune system as well as spreading of the spirochete within the host.

=== '''Host Immune Response Evasion''' ===

BbCRASP-1 has an affinity for Factor H and Factor H-like proteins. Therefore, Factor H binds to BbCRASP-1, which is bound to the outer surface of the spirochete. Because there are multiple BbCRASP-1 proteins on the spirochete, the spirochete is coated with [http://www.uniprot.org/uniprot/CFAH_HUMAN Factor H] and effectively able to infiltrate the host and go undetected in the host's plasma(Bykowski 2007).

=== '''Relation to the Extra Cellular Matrix''' ===

Recently it was found that BbCRASP-1 not only binds to FH and FHL-1 proteins, but it also binds to several other human ligands such as [http://www.uniprot.org/uniprot/BMP2_HUMAN BMP-2] and Extra cellular matrix ligands Collagen I, Collagen III, Collagen IV, fibronectin, laminin, and plasminogen (Hallstrom et al. 2010). As a result of this new finding, BbCRASP-1 is said to advocate the bypassing of the complementary immune system in addition to the pathogenesis of Lyme disease. BbCRASP-1 facilitates binding of “Borrelia burgdoferi” to human cells and tissues, which helps spread the infection (Hallstrom et al. 2010).

<applet load='BBCRASP-12' size='250' frame='true' align='right' caption='BbCRASP-1' scene='Insert optional scene name here' />

== '''Structure''' ==

Sequences of high conservation in the C-terminal regions of the protein’s monomers, <scene name='SB2013_L01gr6/C-terminus/1'>residues 241 to 250</scene> , were of interest as a potential binding site (Cordes F et al. 2005). Previous studies showed that deletion of these sites caused a complete inability of BbCRASP-1 to bind FH and FHL-1 regulators (Kraiczy P et al. 2004). Scientists determined whether the role of the C-terminus region was in maintaining structure or directly functioning as a binding site by mutating <scene name='SB2013_L01gr6/Leucine_246/1'>leucine 246</scene> in the C-terminus region of the dimer to aspartate (Cordes F et al. 2005). This new polar molecule disrupted the hydrophobic interactions in the core of the C-terminal region and caused the entire structure to aggregate as functionally inert mutants. Both the C-terminally truncated and mutated BbCRASP-1 proteins lost their ability to dimerize, inhibiting them from binding to their host’s regulatory factors. It was then concluded that the C-terminus is a structurally sensitive region rather than a direct binding site (Cordes 2005). The C-terminus aids in the stabilization of the dimer by holding the <scene name='SB2013_L01gr6/Monomers/1'>two monomers</scene> in place. The C-terminal of one monomer lies against the <scene name='SB2013_L01gr6/N-terminal_helix/1'>N-terminal half of the helix</scene> of the other and keeps the structure together (Cordes F et al. 2005).

In nature, BbCRASP-1 exists as a dimer. Researchers confirmed this by viewing the presence of pieces of the dimer in solution (Cordes et al. 2005). They viewed the results through analytical ultracentrifugation and saw that dimeric crystals formed. If its dimeric state is threatened, BbCRASP-1 would not be able to function.

Complement Regulator-Acquiring Surface Protein

2013-05-05T00:43:09Z

Dipanshu Walia:

<Structure load='1w33' size='250' frame='true' align='right' caption='BbCRASP-1' scene='Insert optional scene name here' />

== '''Introduction''' ==

Lyme disease is caused by the spirochete ''Borrelia burgdorferi'', and is transferred into vertebrate hosts by zoonotic vectors such as ''Ixodes'' ticks (Bykowski et al. 2007). There are thousands of cases of Lyme disease reported each year, making it a prevalent disease in North America and Eurasia (Cordes et al. 2005). In order for ''B. burgdorferi'' to survive in its host, it evades its immune system through the use of surface proteins. One of the proteins responsible for a successful initial infection is ''Borrelia burgdorferi'' complement regulator-acquiring surface protein 1, or BbCRASP-1 (....). Because BbCRASP-1 binds host complement regulators to the spirochete's outer surface, it remains undetected within the host (Bykowski et al. 2007). BbCRASP-1 specifically binds to complement Factor H (FH) and Factor H-like proteins (FHL-1), which are responsible for the host's immune response and detection of pathogens (Kraiczy et al. 2004). Recently, It was found that Bb-CRASp binds to several other protiens in the extra cellular matrix.

== '''Function''' ==

Bb CRASP-1 can be found on the outer layer of the Lyme disease spirochete and it is essential for the infiltration of the spirochete into the host (Bykowski 2007). BbCRASP-1 provides resistance for the spirochete against the hosts complementary immune system as well as spreading of the spirochete within the host.

=== '''Host Immune Response Evasion''' ===

BbCRASP-1 has an affinity for factor H and Factor H like protiens. Therefore, Factor H binds to Bb-CRASP-1 which is bound to the outer surface of the spirochete. Because there are multiple BbCRASP-1's on the spirochete, the spirochete is covered in [http://www.uniprot.org/uniprot/CFAH_HUMAN Factor H] and effectively able to infiltrate the host and go undetected in the host's plasma(Bykowski 2007).

=== '''Relation to the Extra Cellular Matrix''' ===

More recently it was found that not only does Bb-CRASP bind to FH and FH like proteins, it also bind to several other human ligands such as [http://www.uniprot.org/uniprot/BMP2_HUMAN BMP-2] and Extra cellular matrix ligands Collagen I, Collagen III, Collagen IV, fibronectin, laminin, and plasminogen ( 2010 hallstrom at al.). As a result of this new finding, Bb-CRASP is said to advocate not only the bypassing of the complementary immune system, but the pathogenesis of lyme disease by facilitating “borrelia burgdoferi” to bind to human cells and tissues which helps spread the infection (2010 Hallstrom at al).

<applet load='BBCRASP-12' size='250' frame='true' align='right' caption='BbCRASP-1' scene='Insert optional scene name here' />

== '''Structure''' ==

Sequences of high conservation in the C-terminal regions of the protein’s monomers, <scene name='SB2013_L01gr6/C-terminus/1'>residues 241 to 250</scene> , were of interest as a potential binding site (Cordes F et al. 2005). Previous studies showed that deletion of these sites caused a complete inability of BbCRASP-1 to bind FH and FHL-1 regulators (Kraiczy P et al. 2004). Scientists determined whether the role of the C-terminus region was in maintaining structure or directly functioning as a binding site by mutating <scene name='SB2013_L01gr6/Leucine_246/1'>leucine 246</scene> in the C-terminus region of the dimer to aspartate (Cordes F et al. 2005). This new polar molecule disrupted the hydrophobic interactions in the core of the C-terminal region and caused the entire structure to aggregate as functionally inert mutants. Both the C-terminally truncated and mutated BbCRASP-1 proteins lost their ability to dimerize, inhibiting them from binding to their host’s regulatory factors. It was then concluded that the C-terminus is a structurally sensitive region rather than a direct binding site (Cordes 2005). The C-terminus aids in the stabilization of the dimer by holding the <scene name='SB2013_L01gr6/Monomers/1'>two monomers</scene> in place. The C-terminal of one monomer lies against the <scene name='SB2013_L01gr6/N-terminal_helix/1'>N-terminal half of the helix</scene> of the other and keeps the structure together (Cordes F et al. 2005).

In nature, BbCRASP-1 exists as a dimer. Researchers confirmed this by viewing the presence of pieces of the dimer in solution (Cordes et al. 2005). They viewed the results through analytical ultracentrifugation and saw that dimeric crystals formed. If its dimeric state is threatened, BbCRASP-1 would not be able to function.

Complement Regulator-Acquiring Surface Protein

2013-05-05T00:35:58Z

Dipanshu Walia:

<Structure load='1w33' size='250' frame='true' align='right' caption='Insert caption here' scene='Insert optional scene name here' />== '''Introduction''' ==

Lyme disease is caused by the spirochete ''Borrelia burgdorferi'', and is transferred into vertebrate hosts by zoonotic vectors such as ''Ixodes'' ticks (Bykowski et al. 2007). There are thousands of cases of Lyme disease reported each year, making it a prevalent disease in North America and Eurasia (Cordes et al. 2005). In order for ''B. burgdorferi'' to survive in its host, it evades its immune system through the use of surface proteins. One of the proteins responsible for a successful initial infection is ''Borrelia burgdorferi'' complement regulator-acquiring surface protein 1, or BbCRASP-1 (....). Because BbCRASP-1 binds host complement regulators to the spirochete's outer surface, it remains undetected within the host (Bykowski et al. 2007). BbCRASP-1 specifically binds to complement Factor H (FH) and Factor H-like proteins (FHL-1), which are responsible for the host's immune response and detection of pathogens (Kraiczy et al. 2004). Recently, It was found that Bb-CRASp binds to several other protiens in the extra cellular matrix.

<applet load='BBCRASP-12' size='250' frame='true' align='right' caption='BbCRASP-1' scene='Insert optional scene name here' />

<scene name='SB2013_L01gr6/Bbcrasp1/2'>BbCRASP1</scene>

== '''Function''' ==

Bb CRASP-1 can be found on the outer layer of the Lyme disease spirochete and it is essential for the infiltration of the spirochete into the host (Bykowski 2007). BbCRASP-1 provides resistance for the spirochete against the hosts complementary immune system as well as spreading of the spirochete within the host.

=== '''Host Immune Response Evasion''' ===

BbCRASP-1 has an affinity for factor H and Factor H like protiens. Therefore, Factor H binds to Bb-CRASP-1 which is bound to the outer surface of the spirochete. Because there are multiple BbCRASP-1's on the spirochete, the spirochete is covered in [http://www.uniprot.org/uniprot/CFAH_HUMAN Factor H] and effectively able to infiltrate the host and go undetected in the host's plasma(Bykowski 2007).

=== '''Relation to the Extra Cellular Matrix''' ===

More recently it was found that not only does Bb-CRASP bind to FH and FH like proteins, it also bind to several other human ligands such as [http://www.uniprot.org/uniprot/BMP2_HUMAN BMP-2] and Extra cellular matrix ligands Collagen I, Collagen III, Collagen IV, fibronectin, laminin, and plasminogen ( 2010 hallstrom at al.). As a result of this new finding, Bb-CRASP is said to advocate not only the bypassing of the complementary immune system, but the pathogenesis of lyme disease by facilitating “borrelia burgdoferi” to bind to human cells and tissues which helps spread the infection (2010 Hallstrom at al).

== '''Structure''' ==

Sequences of high conservation in the C-terminal regions of the protein’s monomers, <scene name='SB2013_L01gr6/C-terminus/1'>residues 241 to 250</scene> , were of interest as a potential binding site (Cordes F et al. 2005). Previous studies showed that deletion of these sites caused a complete inability of BbCRASP-1 to bind FH and FHL-1 regulators (Kraiczy P et al. 2004). Scientists determined whether the role of the C-terminus region was in maintaining structure or directly functioning as a binding site by mutating <scene name='SB2013_L01gr6/Leucine_246/1'>leucine 246</scene> in the C-terminus region of the dimer to aspartate (Cordes F et al. 2005). This new polar molecule disrupted the hydrophobic interactions in the core of the C-terminal region and caused the entire structure to aggregate as functionally inert mutants. Both the C-terminally truncated and mutated BbCRASP-1 proteins lost their ability to dimerize, inhibiting them from binding to their host’s regulatory factors. It was then concluded that the C-terminus is a structurally sensitive region rather than a direct binding site (Cordes 2005). The C-terminus aids in the stabilization of the dimer by holding the <scene name='SB2013_L01gr6/Monomers/1'>two monomers</scene> in place. The C-terminal of one monomer lies against the <scene name='SB2013_L01gr6/N-terminal_helix/1'>N-terminal half of the helix</scene> of the other and keeps the structure together (Cordes F et al. 2005).

In nature, BbCRASP-1 exists as a dimer. Researchers confirmed this by viewing the presence of pieces of the dimer in solution (Cordes et al. 2005). They viewed the results through analytical ultracentrifugation and saw that dimeric crystals formed. If its dimeric state is threatened, BbCRASP-1 would not be able to function.

Complement Regulator-Acquiring Surface Protein

2013-05-05T00:34:57Z

Dipanshu Walia:

== '''Introduction''' ==

Lyme disease is caused by the spirochete ''Borrelia burgdorferi'', and is transferred into vertebrate hosts by zoonotic vectors such as ''Ixodes'' ticks (Bykowski et al. 2007). There are thousands of cases of Lyme disease reported each year, making it a prevalent disease in North America and Eurasia (Cordes et al. 2005). In order for ''B. burgdorferi'' to survive in its host, it evades its immune system through the use of surface proteins. One of the proteins responsible for a successful initial infection is ''Borrelia burgdorferi'' complement regulator-acquiring surface protein 1, or BbCRASP-1 (....). Because BbCRASP-1 binds host complement regulators to the spirochete's outer surface, it remains undetected within the host (Bykowski et al. 2007). BbCRASP-1 specifically binds to complement Factor H (FH) and Factor H-like proteins (FHL-1), which are responsible for the host's immune response and detection of pathogens (Kraiczy et al. 2004). Recently, It was found that Bb-CRASp binds to several other protiens in the extra cellular matrix.

<applet load='BBCRASP-12' size='250' frame='true' align='right' caption='BbCRASP-1' scene='Insert optional scene name here' />

<scene name='SB2013_L01gr6/Bbcrasp1/2'>BbCRASP1</scene>

== '''Function''' ==

Bb CRASP-1 can be found on the outer layer of the Lyme disease spirochete and it is essential for the infiltration of the spirochete into the host (Bykowski 2007). BbCRASP-1 provides resistance for the spirochete against the hosts complementary immune system as well as spreading of the spirochete within the host.

=== '''Host Immune Response Evasion''' ===

BbCRASP-1 has an affinity for factor H and Factor H like protiens. Therefore, Factor H binds to Bb-CRASP-1 which is bound to the outer surface of the spirochete. Because there are multiple BbCRASP-1's on the spirochete, the spirochete is covered in [http://www.uniprot.org/uniprot/CFAH_HUMAN Factor H] and effectively able to infiltrate the host and go undetected in the host's plasma(Bykowski 2007).

=== '''Relation to the Extra Cellular Matrix''' ===

More recently it was found that not only does Bb-CRASP bind to FH and FH like proteins, it also bind to several other human ligands such as [http://www.uniprot.org/uniprot/BMP2_HUMAN BMP-2] and Extra cellular matrix ligands Collagen I, Collagen III, Collagen IV, fibronectin, laminin, and plasminogen ( 2010 hallstrom at al.). As a result of this new finding, Bb-CRASP is said to advocate not only the bypassing of the complementary immune system, but the pathogenesis of lyme disease by facilitating “borrelia burgdoferi” to bind to human cells and tissues which helps spread the infection (2010 Hallstrom at al).

== '''Structure''' ==

Sequences of high conservation in the C-terminal regions of the protein’s monomers, <scene name='SB2013_L01gr6/C-terminus/1'>residues 241 to 250</scene> , were of interest as a potential binding site (Cordes F et al. 2005). Previous studies showed that deletion of these sites caused a complete inability of BbCRASP-1 to bind FH and FHL-1 regulators (Kraiczy P et al. 2004). Scientists determined whether the role of the C-terminus region was in maintaining structure or directly functioning as a binding site by mutating <scene name='SB2013_L01gr6/Leucine_246/1'>leucine 246</scene> in the C-terminus region of the dimer to aspartate (Cordes F et al. 2005). This new polar molecule disrupted the hydrophobic interactions in the core of the C-terminal region and caused the entire structure to aggregate as functionally inert mutants. Both the C-terminally truncated and mutated BbCRASP-1 proteins lost their ability to dimerize, inhibiting them from binding to their host’s regulatory factors. It was then concluded that the C-terminus is a structurally sensitive region rather than a direct binding site (Cordes 2005). The C-terminus aids in the stabilization of the dimer by holding the <scene name='SB2013_L01gr6/Monomers/1'>two monomers</scene> in place. The C-terminal of one monomer lies against the <scene name='SB2013_L01gr6/N-terminal_helix/1'>N-terminal half of the helix</scene> of the other and keeps the structure together (Cordes F et al. 2005).

In nature, BbCRASP-1 exists as a dimer. Researchers confirmed this by viewing the presence of pieces of the dimer in solution (Cordes et al. 2005). They viewed the results through analytical ultracentrifugation and saw that dimeric crystals formed. If its dimeric state is threatened, BbCRASP-1 would not be able to function.

Complement Regulator-Acquiring Surface Protein

2013-05-05T00:24:24Z

Dipanshu Walia:

== '''Introduction''' ==

Lyme disease is caused by the spirochete ''Borrelia burgdorferi'', and is transferred into vertebrate hosts by zoonotic vectors such as ''Ixodes'' ticks (Bykowski et al. 2007). There are thousands of cases of Lyme disease reported each year, making it a prevalent disease in North America and Eurasia (Cordes et al. 2005). In order for ''B. burgdorferi'' to survive in its host, it evades its immune system through the use of surface proteins. One of the proteins responsible for a successful initial infection is ''Borrelia burgdorferi'' complement regulator-acquiring surface protein 1, or BbCRASP-1 (....). Because BbCRASP-1 binds host complement regulators to the spirochete's outer surface, it remains undetected within the host (Bykowski et al. 2007). BbCRASP-1 specifically binds to complement Factor H (FH) and Factor H-like proteins (FHL-1), which are responsible for the host's immune response and detection of pathogens (Kraiczy et al. 2004). Recently, It was found that Bb-CRASp binds to several other protiens in the extra cellular matrix.

<applet load='BBCRASP-12' size='250' frame='true' align='right' caption='BbCRASP-1' scene='Insert optional scene name here' />

<scene name='SB2013_L01gr6/Bbcrasp1/2'>BbCRASP1</scene>

== '''Function''' ==

Bb CRASP-1 can be found on the outer layer of the Lyme disease spirochete and it is essential for the infiltration of the spirochete into the host (Bykowski 2007). BbCRASP-1 provides resistance for the spirochete against the hosts complementary immune system as well as spreading of the spirochete within the host.

=== '''Host Immune Response Evasion''' ===

BbCRASP-1 has an affinity for factor H and Factor H like protiens. Therefore, Factor H binds to Bb-CRASP-1 which is bound to the outer surface of the spirochete. Because there are multiple BbCRASP-1's on the spirochete, the spirochete is covered in [http://www.uniprot.org/uniprot/CFAH_HUMAN Factor H] and effectively able to infiltrate the host and go undetected in the host's plasma(Bykowski 2007).

=== '''Relation to the Extra Cellular Matrix''' ===

More recently it was found that not only does Bb-CRASP bind to FH and FH like proteins, it also bind to several other human ligands such as [http://www.uniprot.org/uniprot/BMP2_HUMAN BMP-2] and Extra cellular matrix ligands Collagen I, Collagen III, Collagen IV, fibronectin, laminin, and plasminogen ( 2010 hallstrom at al.). As a result of this new finding, Bb-CRASP is said to advocate not only the bypassing of the complementary immune system, but the pathogenesis of lyme disease by facilitating “borrelia burgdoferi” to bind to human cells and tissues which helps spread the infection (2010 Hallstrom at al).

== '''Structure''' ==

Sequences of high conservation in the C-terminal regions of the protein’s monomers, <scene name='SB2013_L01gr6/C-terminus/1'>residues 241 to 250</scene> , were of interest as a potential binding site (Cordes F et al. 2005). Previous studies showed that deletion of these sites caused a complete inability of BbCRASP-1 to bind FH and FHL-1 regulators (Kraiczy P et al. 2004). Scientists determined whether the role of the C-terminus region was in maintaining structure or directly functioning as a binding site by mutating <scene name='SB2013_L01gr6/Leucine_246/1'>leucine 246</scene> in the C-terminus region of the dimer to aspartate (Cordes F et al. 2005). This new polar molecule disrupted the hydrophobic interactions in the core of the C-terminal region and caused the entire structure to aggregate as functionally inert mutants. Both the C-terminally truncated and mutated BbCRASP-1 proteins lost their ability to dimerize, inhibiting them from binding to their host’s regulatory factors. It was then concluded that the C-terminus is a structurally sensitive region rather than a direct binding site (Cordes 2005). The C-terminus aids in the stabilization of the dimer by holding the <scene name='SB2013_L01gr6/Monomers/1'>two monomers</scene> in place. The C-terminal of one monomer lies against the <scene name='SB2013_L01gr6/Helix/1'>TextToBeDisplayed</scene> N-terminal helix of the other and keeps the structure together (Cordes F et al. 2005).

In nature, BbCRASP-1 exists as a dimer. Researchers confirmed this by viewing the presence of pieces of the dimer in solution (Cordes et al. 2005). They viewed the results through analytical ultracentrifugation and saw that dimeric crystals formed. If its dimeric state is threatened, BbCRASP-1 would not be able to function.

Complement Regulator-Acquiring Surface Protein

2013-05-05T00:12:59Z

Dipanshu Walia:

== '''Introduction''' ==

Lyme disease is caused by the spirochete ''Borrelia burgdorferi'', and is transferred into vertebrate hosts by zoonotic vectors such as ''Ixodes'' ticks (Bykowski et al. 2007). There are thousands of cases of Lyme disease reported each year, making it a prevalent disease in North America and Eurasia (Cordes et al. 2005). In order for ''B. burgdorferi'' to survive in its host, it evades its immune system through the use of surface proteins. One of the proteins responsible for a successful initial infection is ''Borrelia burgdorferi'' complement regulator-acquiring surface protein 1, or BbCRASP-1 (....). Because BbCRASP-1 binds host complement regulators to the spirochete's outer surface, it remains undetected within the host (Bykowski et al. 2007). BbCRASP-1 specifically binds to complement Factor H (FH) and Factor H-like proteins (FHL-1), which are responsible for the host's immune response and detection of pathogens (Kraiczy et al. 2004). Recently, It was found that Bb-CRASp binds to several other protiens in the extra cellular matrix.

<applet load='BBCRASP-12' size='250' frame='true' align='right' caption='BbCRASP-1' scene='Insert optional scene name here' />

<scene name='SB2013_L01gr6/Bbcrasp1/2'>BbCRASP1</scene>

== '''Function''' ==

Bb CRASP-1 can be found on the outer layer of the Lyme disease spirochete and it is essential for the infiltration of the spirochete into the host (Bykowski 2007). BbCRASP-1 provides resistance for the spirochete against the hosts complementary immune system as well as spreading of the spirochete within the host.

=== '''Host Immune Response Evasion''' ===

BbCRASP-1 has an affinity for factor H and Factor H like protiens. Therefore, Factor H binds to Bb-CRASP-1 which is bound to the outer surface of the spirochete. Because there are multiple BbCRASP-1's on the spirochete, the spirochete is covered in [http://www.uniprot.org/uniprot/CFAH_HUMAN Factor H] and effectively able to infiltrate the host and go undetected in the host's plasma(Bykowski 2007).

=== '''Relation to the Extra Cellular Matrix''' ===

More recently it was found that not only does Bb-CRASP bind to FH and FH like proteins, it also bind to several other human ligands such as [http://www.uniprot.org/uniprot/BMP2_HUMAN BMP-2] and Extra cellular matrix ligands Collagen I, Collagen III, Collagen IV, fibronectin, laminin, and plasminogen ( 2010 hallstrom at al.). As a result of this new finding, Bb-CRASP is said to advocate not only the bypassing of the complementary immune system, but the pathogenesis of lyme disease by facilitating “borrelia burgdoferi” to bind to human cells and tissues which helps spread the infection (2010 Hallstrom at al).

== '''Structure''' ==

Sequences of high conservation in the C-terminal regions of the protein’s monomers, <scene name='SB2013_L01gr6/C-terminus/1'>residues 241 to 250</scene> , were of interest as a potential binding site (Cordes F et al. 2005). Previous studies showed that deletion of these sites caused a complete inability of BbCRASP-1 to bind FH and FHL-1 regulators (Kraiczy P et al. 2004). Scientists determined whether the role of the C-terminus region was in maintaining structure or directly functioning as a binding site by mutating <scene name='SB2013_L01gr6/Leucine_246/1'>leucine 246</scene> in the C-terminus region of the dimer to aspartate (Cordes F et al. 2005). This new polar molecule disrupted the hydrophobic interactions in the core of the C-terminal region and caused the entire structure to aggregate as functionally inert mutants. Both the C-terminally truncated and mutated BbCRASP-1 proteins lost their ability to dimerize, inhibiting them from binding to their host’s regulatory factors. It was then concluded that the C-terminus is a structurally sensitive region rather than a direct binding site (Cordes 2005). The C-terminus aids in the stabilization of the dimer by holding the <scene name='SB2013_L01gr6/Monomers/1'>two monomers</scene> in place. The C-terminal of one monomer lies against the N-terminal helix of the other and keeps the structure together (Cordes F et al. 2005).

In nature, BbCRASP-1 exists as a dimer. Researchers confirmed this by viewing the presence of pieces of the dimer in solution (Cordes et al. 2005). They viewed the results through analytical ultracentrifugation and saw that dimeric crystals formed. If its dimeric state is threatened, BbCRASP-1 would not be able to function.

Complement Regulator-Acquiring Surface Protein

2013-05-05T00:11:21Z

Dipanshu Walia:

== '''Introduction''' ==

Lyme disease is caused by the spirochete ''Borrelia burgdorferi'', and is transferred into vertebrate hosts by zoonotic vectors such as ''Ixodes'' ticks (Bykowski et al. 2007). There are thousands of cases of Lyme disease reported each year, making it a prevalent disease in North America and Eurasia (Cordes et al. 2005). In order for ''B. burgdorferi'' to survive in its host, it evades its immune system through the use of surface proteins. One of the proteins responsible for a successful initial infection is ''Borrelia burgdorferi'' complement regulator-acquiring surface protein 1, or BbCRASP-1 (....). Because BbCRASP-1 binds host complement regulators to the spirochete's outer surface, it remains undetected within the host (Bykowski et al. 2007). BbCRASP-1 specifically binds to complement Factor H (FH) and Factor H-like proteins (FHL-1), which are responsible for the host's immune response and detection of pathogens (Kraiczy et al. 2004). Recently, It was found that Bb-CRASp binds to several other protiens in the extra cellular matrix.

<applet load='BBCRASP-12' size='250' frame='true' align='right' caption='BbCRASP-1' scene='Insert optional scene name here' />

<scene name='SB2013_L01gr6/Bbcrasp1/2'>BbCRASP1</scene>

== '''Function''' ==

Bb CRASP-1 can be found on the outer layer of the Lyme disease spirochete and it is essential for the infiltration of the spirochete into the host (Bykowski 2007). BbCRASP-1 provides resistance for the spirochete against the hosts complementary immune system as well as spreading of the spirochete within the host.

=== '''Host Immune Response Evasion''' ===

BbCRASP-1 has an affinity for factor H and Factor H like protiens. Therefore, Factor H binds to Bb-CRASP-1 which is bound to the outer surface of the spirochete. Because there are multiple BbCRASP-1's on the spirochete, the spirochete is covered in [http://www.uniprot.org/uniprot/CFAH_HUMAN Factor H] and effectively able to infiltrate the host and go undetected in the host's plasma(Bykowski 2007).

=== '''Relation to the Extra Cellular Matrix''' ===

More recently it was found that not only does Bb-CRASP bind to FH and FH like proteins, it also bind to several other human ligands such as [http://www.uniprot.org/uniprot/BMP2_HUMAN BMP-2] and Extra cellular matrix ligands Collagen I, Collagen III, Collagen IV, fibronectin, laminin, and plasminogen ( 2010 hallstrom at al.). As a result of this new finding, Bb-CRASP is said to advocate not only the bypassing of the complementary immune system, but the pathogenesis of lyme disease by facilitating “borrelia burgdoferi” to bind to human cells and tissues which helps spread the infection (2010 Hallstrom at al).

== '''Structure''' ==

Sequences of high conservation in the C-terminal regions of the protein’s monomers, <scene name='SB2013_L01gr6/C-terminus/1'>residues 241 to 250</scene> , were of interest as a potential binding site (Cordes F et al. 2005). Previous studies showed that deletion of these sites caused a complete inability of BbCRASP-1 to bind FH and FHL-1 regulators (Kraiczy P et al. 2004). Scientists determined whether the role of the C-terminus region was in maintaining structure or directly functioning as a binding site by mutating <scene name='SB2013_L01gr6/Leucine_246/1'>leucine 246</scene> in the C-terminus region of the dimer (3D Model- gold) to aspartate (Cordes F et al. 2005). This new polar molecule disrupted the hydrophobic interactions in the core of the C-terminal region and caused the entire structure to aggregate as functionally inert mutants. Both the C-terminally truncated and mutated BbCRASP-1 proteins lost their ability to dimerize, inhibiting them from binding to their host’s regulatory factors. It was then concluded that the C-terminus is a structurally sensitive region rather than a direct binding site (Cordes 2005). The C-terminus aids in the stabilization of the dimer by holding the <scene name='SB2013_L01gr6/Monomers/1'>two monomers</scene> in place. The C-terminal of one monomer lies against the N-terminal helix of the other and keeps the structure together (Cordes F et al. 2005).

In nature, BbCRASP-1 exists as a dimer. Researchers confirmed this by viewing the presence of pieces of the dimer in solution (Cordes et al. 2005). They viewed the results through analytical ultracentrifugation and saw that dimeric crystals formed. If its dimeric state is threatened, BbCRASP-1 would not be able to function.

Complement Regulator-Acquiring Surface Protein

2013-05-05T00:06:28Z

Dipanshu Walia:

== '''Introduction''' ==

Lyme disease is caused by the spirochete ''Borrelia burgdorferi'', and is transferred into vertebrate hosts by zoonotic vectors such as ''Ixodes'' ticks (Bykowski et al. 2007). There are thousands of cases of Lyme disease reported each year, making it a prevalent disease in North America and Eurasia (Cordes et al. 2005). In order for ''B. burgdorferi'' to survive in its host, it evades its immune system through the use of surface proteins. One of the proteins responsible for a successful initial infection is ''Borrelia burgdorferi'' complement regulator-acquiring surface protein 1, or BbCRASP-1 (....). Because BbCRASP-1 binds host complement regulators to the spirochete's outer surface, it remains undetected within the host (Bykowski et al. 2007). BbCRASP-1 specifically binds to complement Factor H (FH) and Factor H-like proteins (FHL-1), which are responsible for the host's immune response and detection of pathogens (Kraiczy et al. 2004). Recently, It was found that Bb-CRASp binds to several other protiens in the extra cellular matrix.

<applet load='BBCRASP-12' size='250' frame='true' align='right' caption='BbCRASP-1' scene='Insert optional scene name here' />

<scene name='SB2013_L01gr6/Bbcrasp1/2'>BbCRASP1</scene>

== '''Function''' ==

Bb CRASP-1 can be found on the outer layer of the Lyme disease spirochete and it is essential for the infiltration of the spirochete into the host (Bykowski 2007). BbCRASP-1 provides resistance for the spirochete against the hosts complementary immune system as well as spreading of the spirochete within the host.

=== '''Host Immune Response Evasion''' ===

BbCRASP-1 has an affinity for factor H and Factor H like protiens. Therefore, Factor H binds to Bb-CRASP-1 which is bound to the outer surface of the spirochete. Because there are multiple BbCRASP-1's on the spirochete, the spirochete is covered in [http://www.uniprot.org/uniprot/CFAH_HUMAN Factor H] and effectively able to infiltrate the host and go undetected in the host's plasma(Bykowski 2007).

=== '''Relation to the Extra Cellular Matrix''' ===

More recently it was found that not only does Bb-CRASP bind to FH and FH like proteins, it also bind to several other human ligands such as [http://www.uniprot.org/uniprot/BMP2_HUMAN BMP-2] and Extra cellular matrix ligands Collagen I, Collagen III, Collagen IV, fibronectin, laminin, and plasminogen ( 2010 hallstrom at al.). As a result of this new finding, Bb-CRASP is said to advocate not only the bypassing of the complementary immune system, but the pathogenesis of lyme disease by facilitating “borrelia burgdoferi” to bind to human cells and tissues which helps spread the infection (2010 Hallstrom at al).

== '''Structure''' ==

Sequences of high conservation in the C-terminal regions of the protein’s monomers, <scene name='SB2013_L01gr6/C-terminus/1'>residues 241 to 250</scene> , were of interest as a potential binding site (Cordes F et al. 2005). Previous studies showed that deletion of these sites caused a complete inability of BbCRASP-1 to bind FH and FHL-1 regulators (Kraiczy P et al. 2004). Scientists determined whether the role of the C-terminus region was in maintaining structure or directly functioning as a binding site by mutating <scene name='SB2013_L01gr6/Leucine_246/1'>leucine 246</scene> in the C-terminus region of the dimer (3D Model- gold) to aspartate (Cordes F et al. 2005). This new polar molecule disrupted the hydrophobic interactions in the core of the C-terminal region and caused the entire structure to aggregate as functionally inert mutants. Both the C-terminally truncated and mutated BbCRASP-1 proteins lost their ability to dimerize, inhibiting them from binding to their host’s regulatory factors. It was then concluded that the C-terminus is a structurally sensitive region rather than a direct binding site (Cordes 2005). The C-terminus aids in the stabilization of the dimer by holding the two monomers in place (3D Model- indigo, blue and pale green). The C-terminal of one monomer lies against the N-terminal helix of the other and keeps the structure together (Cordes F et al. 2005).

In nature, BbCRASP-1 exists as a dimer. Researchers confirmed this by viewing the presence of pieces of the dimer in solution (Cordes et al. 2005). They viewed the results through analytical ultracentrifugation and saw that dimeric crystals formed. If its dimeric state is threatened, BbCRASP-1 would not be able to function.

Complement Regulator-Acquiring Surface Protein

2013-05-05T00:02:30Z

Dipanshu Walia:

== '''Introduction''' ==

Lyme disease is caused by the spirochete ''Borrelia burgdorferi'', and is transferred into vertebrate hosts by zoonotic vectors such as ''Ixodes'' ticks (Bykowski et al. 2007). There are thousands of cases of Lyme disease reported each year, making it a prevalent disease in North America and Eurasia (Cordes et al. 2005). In order for ''B. burgdorferi'' to survive in its host, it evades its immune system through the use of surface proteins. One of the proteins responsible for a successful initial infection is ''Borrelia burgdorferi'' complement regulator-acquiring surface protein 1, or BbCRASP-1 (....). Because BbCRASP-1 binds host complement regulators to the spirochete's outer surface, it remains undetected within the host (Bykowski et al. 2007). BbCRASP-1 specifically binds to complement Factor H (FH) and Factor H-like proteins (FHL-1), which are responsible for the host's immune response and detection of pathogens (Kraiczy et al. 2004). Recently, It was found that Bb-CRASp binds to several other protiens in the extra cellular matrix.

<applet load='BBCRASP-12' size='250' frame='true' align='right' caption='BbCRASP-1' scene='Insert optional scene name here' />

<scene name='SB2013_L01gr6/Bbcrasp1/2'>BbCRASP1</scene>

== '''Function''' ==

Bb CRASP-1 can be found on the outer layer of the Lyme disease spirochete and it is essential for the infiltration of the spirochete into the host (Bykowski 2007). BbCRASP-1 provides resistance for the spirochete against the hosts complementary immune system as well as spreading of the spirochete within the host.

=== '''Host Immune Response Evasion''' ===

BbCRASP-1 has an affinity for factor H and Factor H like protiens. Therefore, Factor H binds to Bb-CRASP-1 which is bound to the outer surface of the spirochete. Because there are multiple BbCRASP-1's on the spirochete, the spirochete is covered in [http://www.uniprot.org/uniprot/CFAH_HUMAN Factor H] and effectively able to infiltrate the host and go undetected in the host's plasma(Bykowski 2007).

=== '''Relation to the Extra Cellular Matrix''' ===

More recently it was found that not only does Bb-CRASP bind to FH and FH like proteins, it also bind to several other human ligands such as [http://www.uniprot.org/uniprot/BMP2_HUMAN BMP-2] and Extra cellular matrix ligands Collagen I, Collagen III, Collagen IV, fibronectin, laminin, and plasminogen ( 2010 hallstrom at al.). As a result of this new finding, Bb-CRASP is said to advocate not only the bypassing of the complementary immune system, but the pathogenesis of lyme disease by facilitating “borrelia burgdoferi” to bind to human cells and tissues which helps spread the infection (2010 Hallstrom at al).

== '''Structure''' ==

Sequences of high conservation in the C-terminal regions of the protein’s monomers, residues 241 to 250 (3D Model- indigo), were of interest as a potential binding site (Cordes F et al. 2005). Previous studies showed that deletion of these sites caused a complete inability of BbCRASP-1 to bind FH and FHL-1 regulators (Kraiczy P et al. 2004). Scientists determined whether the role of the C-terminus region was in maintaining structure or directly functioning as a binding site by mutating <scene name='SB2013_L01gr6/Leucine_246/1'>leucine 246</scene> in the C-terminus region of the dimer (3D Model- gold) to aspartate (Cordes F et al. 2005). This new polar molecule disrupted the hydrophobic interactions in the core of the C-terminal region and caused the entire structure to aggregate as functionally inert mutants. Both the C-terminally truncated and mutated BbCRASP-1 proteins lost their ability to dimerize, inhibiting them from binding to their host’s regulatory factors. It was then concluded that the C-terminus is a structurally sensitive region rather than a direct binding site (Cordes 2005). The C-terminus aids in the stabilization of the dimer by holding the two monomers in place (3D Model- indigo, blue and pale green). The C-terminal of one monomer lies against the N-terminal helix of the other and keeps the structure together (Cordes F et al. 2005).

In nature, BbCRASP-1 exists as a dimer. Researchers confirmed this by viewing the presence of pieces of the dimer in solution (Cordes et al. 2005). They viewed the results through analytical ultracentrifugation and saw that dimeric crystals formed. If its dimeric state is threatened, BbCRASP-1 would not be able to function.

Complement Regulator-Acquiring Surface Protein

2013-05-04T23:46:05Z

Dipanshu Walia: /* '''Introduction''' */

== '''Introduction''' ==

Lyme disease is caused by the spirochete ''Borrelia burgdorferi'', and is transferred into vertebrate hosts by zoonotic vectors such as ''Ixodes'' ticks (Bykowski et al. 2007). There are thousands of cases of Lyme disease reported each year, making it a prevalent disease in North America and Eurasia (Cordes et al. 2005). In order for ''B. burgdorferi'' to survive in its host, it evades its immune system through the use of surface proteins. One of the proteins responsible for a successful initial infection is ''Borrelia burgdorferi'' complement regulator-acquiring surface protein 1, or BbCRASP-1 (....). Because BbCRASP-1 binds host complement regulators to the spirochete's outer surface, it remains undetected within the host (Bykowski et al. 2007). BbCRASP-1 specifically binds to complement Factor H (FH) and Factor H-like proteins (FHL-1), which are responsible for the host's immune response and detection of pathogens (Kraiczy et al. 2004). Recently, It was found that Bb-CRASp binds to several other protiens in the extra cellular matrix.

<applet load='BBCRASP-12' size='250' frame='true' align='right' caption='BbCRASP-1' scene='Insert optional scene name here' />

<scene name='SB2013_L01gr6/Bbcrasp1/2'>BbCRASP1</scene>

== '''Function''' ==

Bb CRASP-1 can be found on the outer layer of the Lyme disease spirochete and it is essential for the infiltration of the spirochete into the host (Bykowski 2007). BbCRASP-1 provides resistance for the spirochete against the hosts complementary immune system as well as spreading of the spirochete within the host.

=== '''Host Immune Response Evasion''' ===

BbCRASP-1 has an affinity for factor H and Factor H like protiens. Therefore, Factor H binds to Bb-CRASP-1 which is bound to the outer surface of the spirochete. Because there are multiple BbCRASP-1's on the spirochete, the spirochete is covered in [http://www.uniprot.org/uniprot/CFAH_HUMAN Factor H] and effectively able to infiltrate the host and go undetected in the host's plasma(Bykowski 2007).

=== '''Relation to the Extra Cellular Matrix''' ===

More recently it was found that not only does Bb-CRASP bind to FH and FH like proteins, it also bind to several other human ligands such as [http://www.uniprot.org/uniprot/BMP2_HUMAN BMP-2] and Extra cellular matrix ligands Collagen I, Collagen III, Collagen IV, fibronectin, laminin, and plasminogen ( 2010 hallstrom at al.). As a result of this new finding, Bb-CRASP is said to advocate not only the bypassing of the complementary immune system, but the pathogenesis of lyme disease by facilitating “borrelia burgdoferi” to bind to human cells and tissues which helps spread the infection (2010 Hallstrom at al).

== '''Structure''' ==

Sequences of high conservation in the C-terminal regions of the protein’s monomers, residues 241 to 250 (3D Model- indigo), were of interest as a potential binding site (Cordes F et al. 2005). Previous studies showed that deletion of these sites caused a complete inability of BbCRASP-1 to bind FH and FHL-1 regulators (Kraiczy P et al. 2004). Scientists determined whether the role of the C-terminus region was in maintaining structure or directly functioning as a binding site by mutating leucine 246 in the C-terminus region of the dimer (3D Model- gold) to aspartate (Cordes F et al. 2005). This new polar molecule disrupted the hydrophobic interactions in the core of the C-terminal region and caused the entire structure to aggregate as functionally inert mutants. Both the C-terminally truncated and mutated BbCRASP-1 proteins lost their ability to dimerize, inhibiting them from binding to their host’s regulatory factors. It was then concluded that the C-terminus is a structurally sensitive region rather than a direct binding site (Cordes 2005). The C-terminus aids in the stabilization of the dimer by holding the two monomers in place (3D Model- indigo, blue and pale green). The C-terminal of one monomer lies against the N-terminal helix of the other and keeps the structure together (Cordes F et al. 2005).

In nature, BbCRASP-1 exists as a dimer. Researchers confirmed this by viewing the presence of pieces of the dimer in solution (Cordes et al. 2005). They viewed the results through analytical ultracentrifugation and saw that dimeric crystals formed. If its dimeric state is threatened, BbCRASP-1 would not be able to function.

Complement Regulator-Acquiring Surface Protein

2013-05-04T23:41:04Z

Dipanshu Walia:

== '''Introduction''' ==

Lyme disease is caused by the spirochete ''Borrelia burgdorferi'', and is transferred into vertebrate hosts by zoonotic vectors such as ''Ixodes'' ticks (Bykowski et al. 2007). There are thousands of cases of Lyme disease reported each year, making it a prevalent disease in North America and Eurasia (Cordes et al. 2005). In order for ''B. burgdorferi'' to survive in its host, it evades its immune system through the use of surface proteins. One of the proteins responsible for a successful initial infection is ''Borrelia burgdorferi'' complement regulator-acquiring surface protein 1, or BbCRASP-1 (....). Because BbCRASP-1 binds host complement regulators to the spirochete's outer surface, it remains undetected within the host (Bykowski et al. 2007). BbCRASP-1 specifically binds to complement Factor H (FH) and Factor H-like proteins (FHL-1), which are responsible for the host's immune response and detection of pathogens (Kraiczy et al. 2004). Recently, It was found that Bb-CRASp binds to several other protiens in the extra cellular matrix.

<applet load='BBCRASP-12' size='400' frame='true' align='right' caption='BbCRASP-1' scene='Insert optional scene name here' />

<scene name='SB2013_L01gr6/Bbcrasp1/2'>BbCRASP1</scene>

== '''Function''' ==

Bb CRASP-1 can be found on the outer layer of the Lyme disease spirochete and it is essential for the infiltration of the spirochete into the host (Bykowski 2007). BbCRASP-1 provides resistance for the spirochete against the hosts complementary immune system as well as spreading of the spirochete within the host.

=== '''Host Immune Response Evasion''' ===

BbCRASP-1 has an affinity for factor H and Factor H like protiens. Therefore, Factor H binds to Bb-CRASP-1 which is bound to the outer surface of the spirochete. Because there are multiple BbCRASP-1's on the spirochete, the spirochete is covered in [http://www.uniprot.org/uniprot/CFAH_HUMAN Factor H] and effectively able to infiltrate the host and go undetected in the host's plasma(Bykowski 2007).

=== '''Relation to the Extra Cellular Matrix''' ===

More recently it was found that not only does Bb-CRASP bind to FH and FH like proteins, it also bind to several other human ligands such as [http://www.uniprot.org/uniprot/BMP2_HUMAN BMP-2] and Extra cellular matrix ligands Collagen I, Collagen III, Collagen IV, fibronectin, laminin, and plasminogen ( 2010 hallstrom at al.). As a result of this new finding, Bb-CRASP is said to advocate not only the bypassing of the complementary immune system, but the pathogenesis of lyme disease by facilitating “borrelia burgdoferi” to bind to human cells and tissues which helps spread the infection (2010 Hallstrom at al).

== '''Structure''' ==

Sequences of high conservation in the C-terminal regions of the protein’s monomers, residues 241 to 250 (3D Model- indigo), were of interest as a potential binding site (Cordes F et al. 2005). Previous studies showed that deletion of these sites caused a complete inability of BbCRASP-1 to bind FH and FHL-1 regulators (Kraiczy P et al. 2004). Scientists determined whether the role of the C-terminus region was in maintaining structure or directly functioning as a binding site by mutating leucine 246 in the C-terminus region of the dimer (3D Model- gold) to aspartate (Cordes F et al. 2005). This new polar molecule disrupted the hydrophobic interactions in the core of the C-terminal region and caused the entire structure to aggregate as functionally inert mutants. Both the C-terminally truncated and mutated BbCRASP-1 proteins lost their ability to dimerize, inhibiting them from binding to their host’s regulatory factors. It was then concluded that the C-terminus is a structurally sensitive region rather than a direct binding site (Cordes 2005). The C-terminus aids in the stabilization of the dimer by holding the two monomers in place (3D Model- indigo, blue and pale green). The C-terminal of one monomer lies against the N-terminal helix of the other and keeps the structure together (Cordes F et al. 2005).

In nature, BbCRASP-1 exists as a dimer. Researchers confirmed this by viewing the presence of pieces of the dimer in solution (Cordes et al. 2005). They viewed the results through analytical ultracentrifugation and saw that dimeric crystals formed. If its dimeric state is threatened, BbCRASP-1 would not be able to function.

Complement Regulator-Acquiring Surface Protein

2013-05-04T23:15:43Z

Dipanshu Walia:

== '''Introduction''' ==

Lyme disease is caused by the spirochete ''Borrelia burgdorferi'', and is transferred into vertebrate hosts by zoonotic vectors such as ''Ixodes'' ticks (Bykowski et al. 2007). There are thousands of cases of Lyme disease reported each year, making it a prevalent disease in North America and Eurasia (Cordes et al. 2005). In order for ''B. burgdorferi'' to survive in its host, it evades its immune system through the use of surface proteins. One of the proteins responsible for a successful initial infection is ''Borrelia burgdorferi'' complement regulator-acquiring surface protein 1, or BbCRASP-1 (....). Because BbCRASP-1 binds host complement regulators to the spirochete's outer surface, it remains undetected within the host (Bykowski et al. 2007). BbCRASP-1 specifically binds to complement Factor H (FH) and Factor H-like proteins (FHL-1), which are responsible for the host's immune response and detection of pathogens (Kraiczy et al. 2004). Recently, It was found that Bb-CRASp binds to several other protiens in the extra cellular matrix.

<applet load='BBCRASP-12' size='400' frame='true' align='right' caption='BbCRASP-1' scene='Insert optional scene name here' />

<scene name='SB2013_L01gr6/Bbcrasp1/2'>BbCRASP1</scene>

== '''Function''' ==

Bb CRASP-1 can be found on the outer layer of the Lyme disease spirochete and it is essential for the infiltration of the spirochete into the host (Bykowski 2007). BbCRASP-1 provides resistance for the spirochete against the hosts complementary immune system as well as spreading of the spirochete within the host.

=== '''Host Immune Response Evasion''' ===

BbCRASP-1 has an affinity for factor H and Factor H like protiens. Therefore, Factor H binds to Bb-CRASP-1 which is bound to the outer surface of the spirochete. Because there are multiple BbCRASP-1's on the spirochete, the spirochete is covered in factor H and effectivly able to infiltrate the host and go undetected in the host's plasma(Bykowski 2007).
==== '''Factor H''' ====
Factor H is a complement control protein that can be found in plasma. It functions as a regulator
that directs the complement system to pathogens so they don't harm the host (Alitalo
2002).

=== '''Relation to the Extra Cellular Matrix''' ===

More recently it was found that not only does Bb-CRASP bind to FH and FH like proteins, it also bind to several other human ligands such as BMP-2(bone morphogenetic protein 2) and Extra cellular matrix ligands Collagen I, Collagen III, Collagen IV, fibronectin, laminin, and plasminogen ( 2010 hallstrom at al.). As a result of this new finding, Bb-CRASP is said to advocate not only the bypassing of the complementary immune system, but the pathogenesis of lyme disease by facilitating “borrelia burgdoferi” to bind to human cells and tissues which helps spread the infection (2010 Hallstrom at al).

== '''Structure''' ==

The two monomers (blue & green) are connected together at the C-terminus
(purple) to form the dimer. The C-terminus is of significance because it was thought
to be the binding site of the BbCRASP-1 protein because when the C-terminus
(residues 241-250) was truncated, BbCRASP-1 was no longer able to bind to factor H
(Cordes 2005). Through experimentation, it was suggested that the C-terminus is
actually not the binding sight but a region that controls the structure of the protein.
truncation of the C-terminus (241-250) causes the structure of the protein to change
which causes factor H to not bind. To further test this, a buried leucine(residue 246)
in the C-terminus (yellow) was mutated and replaced by aspartate. this also caused
the protein to not bind to factor H. It was then concluded that the C-terminus is a
structurally sensitive region rather than a direct binding site (cordes 2005).

Complement Regulator-Acquiring Surface Protein

2013-05-04T23:13:55Z

Dipanshu Walia:

== '''Introduction''' ==

Lyme disease is caused by the spirochete ''Borrelia burgdorferi'', and is transferred into vertebrate hosts by zoonotic vectors such as ''Ixodes'' ticks (Bykowski et al. 2007). There are thousands of cases of Lyme disease reported each year, making it a prevalent disease in North America and Eurasia (Cordes et al. 2005). In order for ''B. burgdorferi'' to survive in its host, it evades its immune system through the use of surface proteins. One of the proteins responsible for a successful initial infection is ''Borrelia burgdorferi'' complement regulator-acquiring surface protein 1, or BbCRASP-1 (....). Because BbCRASP-1 binds host complement regulators to the spirochete's outer surface, it remains undetected within the host (Bykowski et al. 2007). BbCRASP-1 specifically binds to complement Factor H (FH) and Factor H-like proteins (FHL-1), which are responsible for the host's immune response and detection of pathogens (Kraiczy et al. 2004). Recently, It was found that Bb-CRASp binds to several other protiens in the extra cellular matrix.

<applet load='BBCRASP-12' size='400' frame='true' align='right' caption='BbCRASP-1' scene='Insert optional scene name here' />

<scene name='SB2013_L01gr6/Bbcrasp1/2'>BbCRASP1</scene>

== '''Function''' ==

Bb CRASP-1 can be found on the outer layer of the Lyme disease spirochete and it is essential for the infiltration of the spirochete into the host (Bykowski 2007). BbCRASP-1 provides resistance for the spirochete against the hosts complementary immune system as well as spreading of the spirochete within the host.

=== '''Bypassing the Host's Immune Response''' ===

BbCRASP-1 has an affinity for factor H and Factor H like protiens. Therefore, Factor H binds to Bb-CRASP-1 which is bound to the outer surface of the spirochete. Because there are multiple BbCRASP-1's on the spirochete, the spirochete is covered in factor H and effectivly able to infiltrate the host and go undetected in the host's plasma(Bykowski 2007).
==== '''Factor H''' ====
Factor H is a complement control protein that can be found in plasma. It functions as a regulator
that directs the complement system to pathogens so they don't harm the host (Alitalo
2002).

=== '''Relation to the Extra Cellular Matrix''' ===

More recently it was found that not only does Bb-CRASP bind to FH and FH like proteins, it also bind to several other human ligands such as BMP-2(bone morphogenetic protein 2) and Extra cellular matrix ligands Collagen I, Collagen III, Collagen IV, fibronectin, laminin, and plasminogen ( 2010 hallstrom at al.). As a result of this new finding, Bb-CRASP is said to advocate not only the bypassing of the complementary immune system, but the pathogenesis of lyme disease by facilitating “borrelia burgdoferi” to bind to human cells and tissues which helps spread the infection (2010 Hallstrom at al).

== '''Structure''' ==

The two monomers (blue & green) are connected together at the C-terminus
(purple) to form the dimer. The C-terminus is of significance because it was thought
to be the binding site of the BbCRASP-1 protein because when the C-terminus
(residues 241-250) was truncated, BbCRASP-1 was no longer able to bind to factor H
(Cordes 2005). Through experimentation, it was suggested that the C-terminus is
actually not the binding sight but a region that controls the structure of the protein.
truncation of the C-terminus (241-250) causes the structure of the protein to change
which causes factor H to not bind. To further test this, a buried leucine(residue 246)
in the C-terminus (yellow) was mutated and replaced by aspartate. this also caused
the protein to not bind to factor H. It was then concluded that the C-terminus is a
structurally sensitive region rather than a direct binding site (cordes 2005).

Complement Regulator-Acquiring Surface Protein

2013-05-04T23:12:55Z

Dipanshu Walia:

== '''Introduction''' ==

Lyme disease is caused by the spirochete ''Borrelia burgdorferi'', and is transferred into vertebrate hosts by zoonotic vectors such as ''Ixodes'' ticks (Bykowski et al. 2007). There are thousands of cases of Lyme disease reported each year, making it a prevalent disease in North America and Eurasia (Cordes et al. 2005). In order for ''B. burgdorferi'' to survive in its host, it evades its immune system through the use of surface proteins. One of the proteins responsible for a successful initial infection is ''Borrelia burgdorferi'' complement regulator-acquiring surface protein 1, or BbCRASP-1 (....). Because BbCRASP-1 binds host complement regulators to the spirochete's outer surface, it remains undetected within the host (Bykowski et al. 2007). BbCRASP-1 specifically binds to complement Factor H (FH) and Factor H-like proteins (FHL-1), which are responsible for the host's immune response and detection of pathogens (Kraiczy et al. 2004). Recently, It was found that Bb-CRASp binds to several other protiens in the extra cellular matrix.

<applet load='BBCRASP-12' size='400' frame='true' align='right' caption='BbCRASP-1' scene='Insert optional scene name here' />

<scene name='SB2013_L01gr6/Bbcrasp1/2'>BbCRASP1</scene>

== '''Function''' ==

Bb CRASP-1 can be found on the outer layer of the Lyme disease spirochete and it is essential for the infiltration of the spirochete into the host (Bykowski 2007). BbCRASP-1 provides resistance for the spirochete against the hosts complementary immune system as well as spreading of the spirochete within the host.

=== '''Bypassing the Host's Immune Response''' ===

BbCRASP-1 has an affinity for factor H and Factor H like protiens. Therefore, Factor H binds to Bb-CRASP-1 which is bound to the outer surface of the spirochete. Because there are multiple BbCRASP-1's on the spirochete, the spirochete is covered in factor H and effectivly able to infiltrate the host and go undetected in the host's plasma(Bykowski 2007).
==== '''Factor H''' ====
Factor H is a complement control protein that can be found in plasma. It functions as a regulator
that directs the complement system to pathogens so they don't harm the host (Alitalo
2002).

=== '''Relation to the Extra Cellular Matrix''' ===

BbCRASP-1 is biologically functional in its dimer form. More recently it was found that not only does Bb-CRASP bind to FH and FH like proteins, it also bind to several other human ligands such as BMP-2(bone morphogenetic protein 2) and Extra cellular matrix ligands Collagen I, Collagen III, Collagen IV, fibronectin, laminin, and plasminogen ( 2010 hallstrom at al.). As a result of this new finding, Bb-CRASP is said to advocate not only the bypassing of the complementary immune system, but the pathogenesis of lyme disease by facilitating “borrelia burgdoferi” to bind to human cells and tissues which helps spread the infection (2010 Hallstrom at al).

== '''Structure''' ==

The two monomers (blue & green) are connected together at the C-terminus
(purple) to form the dimer. The C-terminus is of significance because it was thought
to be the binding site of the BbCRASP-1 protein because when the C-terminus
(residues 241-250) was truncated, BbCRASP-1 was no longer able to bind to factor H
(Cordes 2005). Through experimentation, it was suggested that the C-terminus is
actually not the binding sight but a region that controls the structure of the protein.
truncation of the C-terminus (241-250) causes the structure of the protein to change
which causes factor H to not bind. To further test this, a buried leucine(residue 246)
in the C-terminus (yellow) was mutated and replaced by aspartate. this also caused
the protein to not bind to factor H. It was then concluded that the C-terminus is a
structurally sensitive region rather than a direct binding site (cordes 2005).

Complement Regulator-Acquiring Surface Protein

2013-05-04T21:51:02Z

Dipanshu Walia:

== '''Introduction''' ==

Lyme disease is caused by the spirochete ''Borrelia burgdorferi'', and is transferred into vertebrate hosts by zoonotic vectors such as ''Ixodes'' ticks (Bykowski et al. 2007). There are thousands of cases of Lyme disease reported each year, making it a prevalent disease in North America and Eurasia (Cordes et al. 2005). In order for ''B. burgdorferi'' to survive in its host, it evades its immune system through the use of surface proteins. One of the proteins responsible for a successful initial infection is ''Borrelia burgdorferi'' complement regulator-acquiring surface protein 1, or BbCRASP-1 (....). Because BbCRASP-1 binds host complement regulators to the spirochete's outer surface, it remains undetected within the host (Bykowski et al. 2007). BbCRASP-1 specifically binds to complement Factor H (FH) and Factor H-like proteins (FHL-1), which are responsible for the host's immune response and detection of pathogens (Kraiczy et al. 2004).

<applet load='BBCRASP-12' size='500' frame='true' align='right' caption='BbCRASP-1' scene='Insert optional scene name here' />

<scene name='SB2013_L01gr6/Bbcrasp1/2'>BbCRASP1</scene>

== '''Function''' ==

Bb CRASP-1 can be found on the outer layer of the Lyme disease spirochete and it is essential for the infiltration of the spirochete into the host (Bykowski 2007). BbCRASP-1 provides resistance for the spirochete against the hosts immune system. This is accomplished because BbCRASP-1
has an affinity for factor H and therefore, the spirochete is covered in factor H and
able to infiltrate the host without being recognized (Bykowski 2007). Factor H is a
complement control protein that can be found in plasma. It functions as a regulator
that directs the complement system to pathogens so they don't harm the host (Alitalo
2002). BbCRASP-1 is biologically functional in its dimer form. If BbCRASP-1 isn't
in the dimer form, it does not bind to Factor H ( Cordes 2005). More recently it was found that not only does Bb-CRASP bind to FH and FH like proteins, it also bind to several other human ligands such as BMP-2(bone morphogenetic protein 2) and Extra cellular matrix ligands Collagen I, Collagen III, Collagen IV, fibronectin, laminin, and plasminogen ( 2010 hallstrom at al.). As a result of this new finding, Bb-CRASP is said to advocate not only the bypassing of the complementary immune system, but the pathogenesis of lyme disease by facilitating “borrelia burgdoferi” to bind to human cells and tissues which helps spread the infection (2010 Hallstrom at al).

== '''Structure''' ==

The two monomers (blue & green) are connected together at the C-terminus
(purple) to form the dimer. The C-terminus is of significance because it was thought
to be the binding site of the BbCRASP-1 protein because when the C-terminus
(residues 241-250) was truncated, BbCRASP-1 was no longer able to bind to factor H
(Cordes 2005). Through experimentation, it was suggested that the C-terminus is
actually not the binding sight but a region that controls the structure of the protein.
truncation of the C-terminus (241-250) causes the structure of the protein to change
which causes factor H to not bind. To further test this, a buried leucine(residue 246)
in the C-terminus (yellow) was mutated and replaced by aspartate. this also caused
the protein to not bind to factor H. It was then concluded that the C-terminus is a
structurally sensitive region rather than a direct binding site (cordes 2005).

Complement Regulator-Acquiring Surface Protein

2013-05-04T21:45:00Z

Dipanshu Walia: /* '''Function''' */

Complement Regulator-Acquiring Surface Protein

2013-05-04T21:41:38Z

Dipanshu Walia: /* '''Introduction''' */

Complement Regulator-Acquiring Surface Protein

2013-05-04T21:26:52Z

Dipanshu Walia:

== '''Introduction''' ==

Lyme disease is caused by the spirochete ''Borrelia burgdorferi''. It is transferred into vertebrate hosts by zoonotic vectors, such as ''Ixodes'' ticks (Bykowski et al. 2007). There are thousands of cases reported each year, making it a prevalent disease in North America and Eurasia (Cordes et al. 2005). One of the ways ''B. burgdorferi'' is able to survive in its host is by evading its immune system. A protein responsible for a successful initial infection is ''Borrelia burgdorferi'' complement regulator-aquiring surface protein 1, or BbCRASP-1 (....). BbCRASP-1 binds host complement regulators to the spirochete's to remain undetected within the host (Bykowski et al. 2007). BbCRASP-1 specifically binds complement Factor H and Factor H-like proteins, which are responsible for an organism's detection of pathogens (Kraiczy et al. 2004).

<applet load='BBCRASP-12' size='500' frame='true' align='right' caption='BbCRASP-1' scene='Insert optional scene name here' />

<scene name='SB2013_L01gr6/Bbcrasp1/2'>BbCRASP1</scene>

== '''Function''' ==

Shown above is the Borrelia burgdorferi Complement Regulator-Acquiring
Surface Protein or Bb CRASP-1 for short. Bb CRASP-1 can be found on the outer
layer of the Lyme disease spirochete and it is essential for the infiltration of the spirochete into the host (Bykowski 2007). BbCRASP-1 provides resistance for the spirochete against the hosts immune system. This is accomplished because BbCRASP-1
has an affinity for factor H and therefore, the spirochete is covered in factor H and
able to infiltrate the host without being recognized (Bykowski 2007). Factor H is a
complement control protein that can be found in plasma. It functions as a regulator
that directs the complement system to pathogens so they don't harm the host (Alitalo
2002). BbCRASP-1 is biologically functional in its dimer form. If BbCRASP-1 isn't
in the dimer form, it does not bind to Factor H ( Cordes 2005). More recently it was found that not only does Bb-CRASP bind to FH and FH like proteins, it also bind to several other human ligands such as BMP-2(bone morphogenetic protein 2) and Extra cellular matrix ligands Collagen I, Collagen III, Collagen IV, fibronectin, laminin, and plasminogen ( 2010 hallstrom at al.). As a result of this new finding, Bb-CRASP is said to advocate not only the bypassing of the complementary immune system, but the pathogenesis of lyme disease by facilitating “borrelia burgdoferi” to bind to human cells and tissues which helps spread the infection (2010 Hallstrom at al).