Complement Regulator-Acquiring Surface Protein - Revision history

Michal Harel at 11:36, 4 February 2025

2025-02-04T11:36:10Z

← Older revision		Revision as of 11:36, 4 February 2025
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	**[[4bg0]] – BbCRASP-2 residues 23-236<br />		**[[4bg0]] – BbCRASP-2 residues 23-236<br />
	**[[4cbe]] – BbCRASP-2 residues 23-236<br />		**[[4cbe]] – BbCRASP-2 residues 23-236<br />
	**[[6atg]] – BbCRASP-2 residues 23-236 + complement factor H<br />		**[[6atg]], [[9f7i]] – BbCRASP-2 residues 23-236 + complement factor H<br />
	**[[5y4m]] – BbCRASP-2 DISK domain residues 35-181 <br />		**[[5y4m]] – BbCRASP-2 DISK domain residues 35-181 <br />

Michal Harel at 07:38, 6 June 2024

2024-06-06T07:38:07Z

← Older revision		Revision as of 07:38, 6 June 2024
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	== '''Introduction''' ==		== '''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.		[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.

	*'''BbCRASP-2''' interacts preferentially with factor H<ref> PMID: 11385611</ref>.		*'''BbCRASP-2''' interacts preferentially with factor H<ref> PMID: 11385611</ref>.
			*'''BbCRASP-3''' and '''BbCRASP-4''' belong to different strains of ''Borrelia burgdorferi''<ref> PMID: 23219363</ref>.
	== '''Structure''' ==		== '''Structure''' ==

Michal Harel at 07:22, 6 June 2024

2024-06-06T07:22:43Z

← Older revision		Revision as of 07:22, 6 June 2024
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	[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.		[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.

	*'''BbCRASP-2''' interacts preferentially with factor H<ref PMID: 11385611</ref>.		*'''BbCRASP-2''' interacts preferentially with factor H<ref> PMID: 11385611</ref>.

	== '''Structure''' ==		== '''Structure''' ==

Michal Harel at 07:19, 6 June 2024

2024-06-06T07:19:46Z

← Older revision		Revision as of 07:19, 6 June 2024
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	[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.		[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.

	*'''BbCRASP-2''' interacts preferentially with factor H<ref PMID: 11385611</ref>.		*'''BbCRASP-2''' interacts preferentially with factor H<ref PMID: 11385611</ref>.

Michal Harel at 07:18, 6 June 2024

2024-06-06T07:18:56Z

← Older revision		Revision as of 07:18, 6 June 2024
Line 3:		Line 3:

	[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.		[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.
			*'''BbCRASP-2''' interacts preferentially with factor H<ref PMID: 11385611</ref>.

	== '''Structure''' ==		== '''Structure''' ==

Michal Harel at 08:19, 7 July 2020

2020-07-07T08:19:28Z

← Older revision		Revision as of 08:19, 7 July 2020
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	*CRASP-2 or CspZ		*CRASP-2 or CspZ

	**[[4bg0]] – BbCRASP-2<br />		**[[4bg0]] – BbCRASP-2 residues 23-236<br />
	**[[4cbe]] – BbCRASP-2 residues 23-236<br />		**[[4cbe]] – BbCRASP-2 residues 23-236<br />
	**[[6atg]] – BbCRASP-2 + complement factor H<br />		**[[6atg]] – BbCRASP-2 residues 23-236 + complement factor H<br />
			**[[5y4m]] – BbCRASP-2 DISK domain residues 35-181 <br />

	*CRASP-3 or ErpP		*CRASP-3 or ErpP

	**[[4bob]] – BbCRASP-3 ~~residues 27-186~~<br />		**[[4bob]] – BbCRASP-3 DISK domain<br />

	*CRASP-4 or ErpC		*CRASP-4 or ErpC

	**[[4bod]], [[4bxm]], [[4bf3]] – BbCRASP-4 ~~residues 27-179~~<br />		**[[4bod]], [[4bxm]], [[4bf3]] – BbCRASP-4 DISK domain<br />

Alexander Berchansky at 13:06, 15 May 2019

2019-05-15T13:06:38Z

← Older revision		Revision as of 13:06, 15 May 2019
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	<~~Structure~~ load='1w33' size='~~250~~' ~~frame~~='~~true~~' ~~align~~='~~right~~' caption='BbCRASP-1 (PDB code [[1w33]])' ~~scene='SB2013_L01gr6/Bbcrasp-1_no_spacefill/2' /~~>		<StructureSection load='1w33' size='350' side='right' scene='SB2013_L01gr6/Bbcrasp-1_no_spacefill/2' caption='BbCRASP-1 (PDB code [[1w33]])'>

	== '''Introduction''' ==		== '''Introduction''' ==

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	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 mount an effective defense against the invading spirochete.		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 mount an effective defense against the invading spirochete.
			</StructureSection>
	== '''3D structure of BbCRASP''' ==		== '''3D structure of BbCRASP''' ==

Michal Harel at 08:43, 15 May 2019

2019-05-15T08:43:52Z

← Older revision		Revision as of 08:43, 15 May 2019
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	<references />		<references />
			[[Category:Topic Page]]

Michal Harel at 08:42, 15 May 2019

2019-05-15T08:42:16Z

← Older revision		Revision as of 08:42, 15 May 2019
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	{{#tree:id=OrganizedByTopic\|openlevels=0\|		{{#tree:id=OrganizedByTopic\|openlevels=0\|

	*CRASP-1		*CRASP-1 or Spa

	**[[1w33]], [[1w3z]], [[4bl4]], [[5a2u]] - BbCRASP-1 extracellular domain - ''Borrelia burgdorferi''<br />		**[[1w33]], [[1w3z]], [[4bl4]], [[5a2u]] - BbCRASP-1 extracellular domain - ''Borrelia burgdorferi''<br />

	*CRASP-2		*CRASP-2 or CspZ

	**[[4bg0]] – BbCRASP-2<br />		**[[4bg0]] – BbCRASP-2<br />
	**[[4cbe]] – BbCRASP-2 residues 23-236<br />		**[[4cbe]] – BbCRASP-2 residues 23-236<br />
			**[[6atg]] – BbCRASP-2 + complement factor H<br />

			*CRASP-3 or ErpP

			**[[4bob]] – BbCRASP-3 residues 27-186<br />

			*CRASP-4 or ErpC

			**[[4bod]], [[4bxm]], [[4bf3]] – BbCRASP-4 residues 27-179<br />


	}}		}}

Michal Harel at 09:53, 15 April 2018

2018-04-15T09:53:19Z

← Older revision		Revision as of 09:53, 15 April 2018
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	*CRASP-1		*CRASP-1

	**[[1w33]], [[1w3z]], [[5a2u]] - BbCRASP-1 extracellular domain - ''Borrelia burgdorferi''<br />		**[[1w33]], [[1w3z]], [[4bl4]], [[5a2u]] - BbCRASP-1 extracellular domain - ''Borrelia burgdorferi''<br />

	*CRASP-2		*CRASP-2