Complement Regulator-Acquiring Surface Protein: Difference between revisions
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== '''Introduction''' == | == '''Introduction''' == | ||
Lyme disease is caused by the spirochete ''Borrelia burgdorferi'', and is transferred into vertebrate hosts by zoonotic vectors such as ''Ixodes'' ticks (Bykowski et al. 2007). There are thousands of cases of Lyme disease reported each year, making it a prevalent disease in North America and Eurasia (Cordes et al. 2005). In order for ''B. burgdorferi'' to survive in its host, it evades | Lyme disease is caused by the spirochete ''Borrelia burgdorferi'', and is transferred into vertebrate hosts by zoonotic vectors such as ''Ixodes'' ticks (Bykowski et al. 2007). There are thousands of cases of Lyme disease reported each year, making it a prevalent disease in North America and Eurasia (Cordes et al. 2005). In order for ''B. burgdorferi'' to survive in its host, it evades the host's immune system through the use of complement regulator-acquiring surface proteins. One such protein responsible for a successful initial infection is ''Borrelia burgdorferi'' complement regulator-acquiring surface protein 1, or BbCRASP-1 (Bykowski et al. 2007). Because BbCRASP-1 binds host complement regulators to the spirochete's outer surface, ''B. burgdorferi'' remains undetected within the host (Bykowski et al. 2007). BbCRASP-1 specifically binds to complement Factor H (FH) and Factor H-like proteins (FHL-1), which are responsible for the host's immune response and detection of pathogens (Kraiczy et al. 2004). Recently, it was found that BbCRASP-1 binds to several other proteins in the extra cellular matrix of a human cell. | ||
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== '''Function''' == | == '''Function''' == | ||
Bb CRASP-1 can be found on the outer layer of the Lyme disease spirochete and | Bb CRASP-1 can be found on the outer layer of the Lyme disease spirochete and is essential for the infiltration of the spirochete into the host (Bykowski 2007). BbCRASP-1 provides resistance for the spirochete against the host's complementary immune system as well as spreading of the spirochete within the host. | ||
=== '''Host Immune Response Evasion''' === | === '''Host Immune Response Evasion''' === | ||
BbCRASP-1 has an affinity for | BbCRASP-1 has an affinity for Factor H and Factor H-like proteins. Therefore, Factor H binds to BbCRASP-1, which is bound to the outer surface of the spirochete. Because there are multiple BbCRASP-1 proteins on the spirochete, the spirochete is coated with [http://www.uniprot.org/uniprot/CFAH_HUMAN Factor H] and effectively able to infiltrate the host and go undetected in the host's plasma(Bykowski 2007). | ||
=== '''Relation to the Extra Cellular Matrix''' === | === '''Relation to the Extra Cellular Matrix''' === | ||
Recently it was found that BbCRASP-1 not only binds to FH and FHL-1 proteins, but it also binds to several other human ligands such as [http://www.uniprot.org/uniprot/BMP2_HUMAN BMP-2] and Extra cellular matrix ligands Collagen I, Collagen III, Collagen IV, fibronectin, laminin, and plasminogen (Hallstrom et al. 2010). As a result of this new finding, BbCRASP-1 is said to advocate the bypassing of the complementary immune system in addition to the pathogenesis of Lyme disease. BbCRASP-1 facilitates binding of “Borrelia burgdoferi” to human cells and tissues, which helps spread the infection (Hallstrom et al. 2010). | |||
Revision as of 04:05, 5 May 2013
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IntroductionIntroduction
Lyme disease is caused by the spirochete Borrelia burgdorferi, and is transferred into vertebrate hosts by zoonotic vectors such as Ixodes ticks (Bykowski et al. 2007). There are thousands of cases of Lyme disease reported each year, making it a prevalent disease in North America and Eurasia (Cordes et al. 2005). In order for B. burgdorferi to survive in its host, it evades the host's immune system through the use of complement regulator-acquiring surface proteins. One such protein responsible for a successful initial infection is Borrelia burgdorferi complement regulator-acquiring surface protein 1, or BbCRASP-1 (Bykowski et al. 2007). Because BbCRASP-1 binds host complement regulators to the spirochete's outer surface, B. burgdorferi remains undetected within the host (Bykowski et al. 2007). BbCRASP-1 specifically binds to complement Factor H (FH) and Factor H-like proteins (FHL-1), which are responsible for the host's immune response and detection of pathogens (Kraiczy et al. 2004). Recently, it was found that BbCRASP-1 binds to several other proteins in the extra cellular matrix of a human cell.
FunctionFunction
Bb CRASP-1 can be found on the outer layer of the Lyme disease spirochete and is essential for the infiltration of the spirochete into the host (Bykowski 2007). BbCRASP-1 provides resistance for the spirochete against the host's complementary immune system as well as spreading of the spirochete within the host.
Host Immune Response EvasionHost 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 Factor H and effectively able to infiltrate the host and go undetected in the host's plasma(Bykowski 2007).
Relation to the Extra Cellular MatrixRelation 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 BMP-2 and Extra cellular matrix ligands Collagen I, Collagen III, Collagen IV, fibronectin, laminin, and plasminogen (Hallstrom et al. 2010). As a result of this new finding, BbCRASP-1 is said to advocate the bypassing of the complementary immune system in addition to the pathogenesis of Lyme disease. BbCRASP-1 facilitates binding of “Borrelia burgdoferi” to human cells and tissues, which helps spread the infection (Hallstrom et al. 2010).
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StructureStructure
Sequences of high conservation in the C-terminal regions of the protein’s monomers, , were of interest as a potential binding site (Cordes F et al. 2005). Previous studies showed that deletion of these sites caused a complete inability of BbCRASP-1 to bind FH and FHL-1 regulators (Kraiczy P et al. 2004). Scientists determined whether the role of the C-terminus region was in maintaining structure or directly functioning as a binding site by mutating in the C-terminus region of the dimer to aspartate (Cordes F et al. 2005). This new polar molecule disrupted the hydrophobic interactions in the core of the C-terminal region and caused the entire structure to aggregate as functionally inert mutants. Both the C-terminally truncated and mutated BbCRASP-1 proteins lost their ability to dimerize, inhibiting them from binding to their host’s regulatory factors. It was then concluded that the C-terminus is a structurally sensitive region rather than a direct binding site (Cordes 2005). The C-terminus aids in the stabilization of the dimer by holding the in place. The C-terminal of one monomer lies against the of the other and keeps the structure together (Cordes F et al. 2005).
In nature, BbCRASP-1 exists as a dimer. Researchers confirmed this by viewing the presence of pieces of the dimer in solution (Cordes et al. 2005). They viewed the results through analytical ultracentrifugation and saw that dimeric crystals formed. If its dimeric state is threatened, BbCRASP-1 would not be able to function.