Proteopedia - User contributions [en]

Complement Regulator-Acquiring Surface Protein

2013-05-06T17:41:20Z

Kerry Brathwaite: /* '''Importance of the C-terminus''' */

<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/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

2013-05-06T17:40:00Z

Kerry Brathwaite:

<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_246/1'>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>. <scene name='SB2013_L01gr6/Leucine_246/2'>TextToBeDisplayed</scene>

=== '''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

2013-05-06T17:36:34Z

Kerry Brathwaite: /* '''Structure''' */

<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_246/1'>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

2013-05-06T16:42:47Z

Kerry Brathwaite: /* '''Introduction''' */

<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>. 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

2013-05-06T05:23:07Z

Kerry Brathwaite: /* '''Importance of the C-terminus''' */

<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, 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

2013-05-06T05:20:18Z

Kerry Brathwaite: /* '''Importance of the C-terminus''' */

<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, 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/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

2013-05-06T05:17:59Z

Kerry Brathwaite: /* '''Importance of the C-terminus''' */

<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, 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 region 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/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

2013-05-06T05:16:08Z

Kerry Brathwaite: /* '''Importance of the C-terminus''' */

<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, 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 region was determined 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_ribbon/1'>N-terminal half of the E 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>. 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

2013-05-06T05:12:12Z

Kerry Brathwaite: /* '''Other Potential Binding Sites''' */

<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, 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>. 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_ribbon/1'>N-terminal half of the E 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>. 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

2013-05-06T05:05:44Z

Kerry Brathwaite: /* '''Discussion''' */

<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, 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>. 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_ribbon/1'>N-terminal half of the E 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 among various Borrelia CRASP-1 proteins encoded by the same gene. They saw that 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

2013-05-06T05:01:34Z

Kerry Brathwaite: /* '''Other Potential Binding Sites''' */

<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, 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>. 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_ribbon/1'>N-terminal half of the E 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 among various Borrelia CRASP-1 proteins encoded by the same gene. They saw that 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

2013-05-06T04:15:36Z

Kerry Brathwaite:

<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, 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>. 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_ribbon/1'>N-terminal half of the E 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 among various Borrelia CRASP-1 proteins encoded by the same gene. They saw that the greatest homologous region was clustered on the center of the <scene name='SB2013_L01gr6/Pocket_region/3'>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

2013-05-06T03:46:17Z

Kerry Brathwaite:

<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, 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>. 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_ribbon/1'>N-terminal half of the E 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>.

== '''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

2013-05-06T03:43:13Z

Kerry Brathwaite: /* '''Introduction''' */

<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, 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>. 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_ribbon/1'>N-terminal half of the E 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>.

== '''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

2013-05-06T03:41:03Z

Kerry Brathwaite: /* '''Importance of the C-terminus''' */

<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_ribbon/1'>N-terminal half of the E 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>.

== '''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

2013-05-06T03:36:51Z

Kerry Brathwaite: /* '''Future Studies''' */

<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 E 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>. <scene name='SB2013_L01gr6/N-terminal_helix_ribbon/1'>TextToBeDisplayed</scene>

=== '''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>.

== '''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

2013-05-06T03:35:17Z

Kerry Brathwaite: /* '''Relation to the Extra Cellular Matrix''' */

<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 E 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>. <scene name='SB2013_L01gr6/N-terminal_helix_ribbon/1'>TextToBeDisplayed</scene>

=== '''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>.

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

Further work needs to be done to determine the complement regulator protein 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

2013-05-06T03:29:08Z

Kerry Brathwaite: /* '''Importance of the C-terminus''' */

<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 E 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>. <scene name='SB2013_L01gr6/N-terminal_helix_ribbon/1'>TextToBeDisplayed</scene>

=== '''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>.

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

Further work needs to be done to determine the complement regulator protein 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

2013-05-06T03:21:56Z

Kerry Brathwaite: /* Future Studies */

<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>. <scene name='SB2013_L01gr6/N-terminal_helix_ribbon/1'>TextToBeDisplayed</scene>

=== '''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>.

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

Further work needs to be done to determine the complement regulator protein 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

2013-05-06T03:21:07Z

Kerry Brathwaite:

<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>. <scene name='SB2013_L01gr6/N-terminal_helix_ribbon/1'>TextToBeDisplayed</scene>

=== '''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>.

== Future Studies ==

Further work needs to be done to determine the complement regulator protein 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

2013-05-06T02:52:44Z

Kerry Brathwaite:

<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>. <scene name='SB2013_L01gr6/N-terminal_helix_ribbon/1'>TextToBeDisplayed</scene>

=== '''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

2013-05-06T01:04:01Z

Kerry Brathwaite:

<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/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

2013-05-05T20:52:29Z

Kerry Brathwaite:

<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

2013-04-26T21:26:52Z

Kerry Brathwaite:

== '''Background''' ==

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>

Complement Regulator-Acquiring Surface Protein

2013-04-26T21:25:45Z

Kerry Brathwaite:

'''Background'''

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>

Complement Regulator-Acquiring Surface Protein

2013-04-26T21:23:53Z

Kerry Brathwaite:

Background

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>

Complement Regulator-Acquiring Surface Protein

2013-04-22T20:52:09Z

Kerry Brathwaite:

<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>

Complement Regulator-Acquiring Surface Protein

2013-04-22T20:49:57Z

Kerry Brathwaite:

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

<scene name='SB2013_L01gr6/Bbcrasp/1'>TextToBeDisplayed</scene>

Complement Regulator-Acquiring Surface Protein

2013-04-22T20:48:19Z

Kerry Brathwaite:

<applet load='Bbcrasp-12' size='500' frame='true' align='right' caption='Insert caption here' scene='BbCRASP1' />

<scene name='SB2013_L01gr6/Bbcrasp/1'>TextToBeDisplayed</scene>

Complement Regulator-Acquiring Surface Protein

2013-04-22T20:38:00Z

Kerry Brathwaite:

<scene name='SB2013_L01gr6/Bbcrasp/1'>TextToBeDisplayed</scene>

Complement Regulator-Acquiring Surface Protein

2013-04-22T20:32:27Z

Kerry Brathwaite:

<scene name='SB2013_L01gr6/Bbcrasp1/1'>TextToBeDisplayed</scene>

Complement Regulator-Acquiring Surface Protein

2013-04-22T20:10:11Z

Kerry Brathwaite:

'''Hello World, this is my proteopedia page! wooooohoooooooo'''

<applet load='T0499.pdb' size='500' frame='true' align='right' caption='Im a MEGA protein T0499!!!' scene='Insert optional scene name here' />

[[Image:MW_Folding_Simulations.gif]]

<scene name='colorGROUP'>N to C terminus</scene>
Red
<scene name='colorSTRUCTURE'>structure</scene>
Yellow

<Structure load='1acj' size='500' frame='true' align='right' caption='Insert caption here' scene='Insert optional scene name here' />
<scene name='SB2013_L01gr6/Tacrine/2'>Zoom in to view Tacrine</scene>

Complement Regulator-Acquiring Surface Protein

2013-04-22T20:09:14Z

Kerry Brathwaite:

Complement Regulator-Acquiring Surface Protein

2013-04-22T19:54:22Z

Kerry Brathwaite:

Complement Regulator-Acquiring Surface Protein

2013-04-22T19:52:58Z

Kerry Brathwaite:

Complement Regulator-Acquiring Surface Protein

2013-04-22T19:50:19Z

Kerry Brathwaite:

Complement Regulator-Acquiring Surface Protein

2013-04-22T19:48:43Z

Kerry Brathwaite:

Complement Regulator-Acquiring Surface Protein

2013-04-22T19:47:13Z

Kerry Brathwaite:

'''Hello World, this is my proteopedia page! wooooohoooooooo'''

<applet load='1acj' size='500' frame='true' align='right' caption='Im a MEGA protein!' scene='Insert optional scene name here' />

[[Image:MW_Folding_Simulations.gif]]

Complement Regulator-Acquiring Surface Protein

2013-04-22T19:45:40Z

Kerry Brathwaite:

'''Hello World, this is my proteopedia page! wooooohoooooooo'''

<applet load='1acj' size='500' frame='true' align='right' caption='Im a MEGA protein!' scene='Insert optional scene name here' />

Complement Regulator-Acquiring Surface Protein

2013-04-22T19:45:17Z

Kerry Brathwaite:

'''Hello World, this is my proteopedia page! wooooohoooooooo'''

<applet load='1acj' size='1000' frame='true' align='right' caption='Im a MEGA protein!' scene='Insert optional scene name here' />

Complement Regulator-Acquiring Surface Protein

2013-04-22T19:44:42Z

Kerry Brathwaite:

'''Hello World, this is my proteopedia page! wooooohoooooooo'''

<applet load='1acj' size='1000' frame='true' align='right' caption='Im a protein!' scene='Insert optional scene name here' />

Complement Regulator-Acquiring Surface Protein

2013-04-22T19:43:56Z

Kerry Brathwaite:

'''Hello World, this is my proteopedia page! wooooohoooooooo'''

<applet load='1acj' size='400' frame='true' align='right' caption='I'm a protein!' scene='Insert optional scene name here' />

Complement Regulator-Acquiring Surface Protein

2013-04-22T19:42:53Z

Kerry Brathwaite:

'''Hello World, this is my proteopedia page! wooooohoooooooo'''

<applet load='1acj' size='1000' frame='true' align='right' caption='I'm a protein!' scene='Insert optional scene name here' />

Complement Regulator-Acquiring Surface Protein

2013-04-22T19:40:59Z

Kerry Brathwaite:

'''Hello World, this is my proteopedia page! wooooohoooooooo'''

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

Complement Regulator-Acquiring Surface Protein

2013-04-22T19:38:07Z

Kerry Brathwaite:

'''Hello World, this is my proteopedia page! wooooohoooooooo'''

Complement Regulator-Acquiring Surface Protein

2013-04-22T19:37:56Z

Kerry Brathwaite:

Hello World, this is my proteopedia page! wooooohoooooooo

Complement Regulator-Acquiring Surface Protein

2013-04-22T19:36:32Z

Kerry Brathwaite:

Hello World, this is my proteopedia page! wooooohoooooooo

Complement Regulator-Acquiring Surface Protein

2013-04-22T19:24:15Z

Kerry Brathwaite: /* Structure */

== Structure ==
<StructureSection load='1dq8' size='350' side='right' caption='Structure of HMG-CoA reductase (PDB entry [[1W33]])' scene=''>
Anything in this section will appear adjacent to the 3D structure and will be scrollable.

</StructureSection>

Complement Regulator-Acquiring Surface Protein

2013-04-22T19:23:38Z

Kerry Brathwaite: New page: == Structure == <StructureSection load='1dq8' size='350' side='right' caption='Structure of HMG-CoA reductase (PDB entry 1dq8)' scene=''> Anything in this section will appear adjacent ...

== Structure ==
<StructureSection load='1dq8' size='350' side='right' caption='Structure of HMG-CoA reductase (PDB entry [[1dq8]])' scene=''>
Anything in this section will appear adjacent to the 3D structure and will be scrollable.

</StructureSection>