Complement Regulator-Acquiring Surface Protein: Difference between revisions
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2002). BbCRASP-1 is biologically functional in its dimer form. If BbCRASP-1 isn't | 2002). BbCRASP-1 is biologically functional in its dimer form. If BbCRASP-1 isn't | ||
in the dimer form, it does not bind to Factor H ( Cordes 2005). More recently it was found that not only does Bb-CRASP bind to FH and FH like proteins, it also bind to several other human ligands such as BMP-2(bone morphogenetic protein 2) and Extra cellular matrix ligands Collagen I, Collagen III, Collagen IV, fibronectin, laminin, and plasminogen ( 2010 hallstrom at al.). As a result of this new finding, Bb-CRASP is said to advocate not only the bypassing of the complementary immune system, but the pathogenesis of lyme disease by facilitating “borrelia burgdoferi” to bind to human cells and tissues which helps spread the infection (2010 Hallstrom at al). | in the dimer form, it does not bind to Factor H ( Cordes 2005). More recently it was found that not only does Bb-CRASP bind to FH and FH like proteins, it also bind to several other human ligands such as BMP-2(bone morphogenetic protein 2) and Extra cellular matrix ligands Collagen I, Collagen III, Collagen IV, fibronectin, laminin, and plasminogen ( 2010 hallstrom at al.). As a result of this new finding, Bb-CRASP is said to advocate not only the bypassing of the complementary immune system, but the pathogenesis of lyme disease by facilitating “borrelia burgdoferi” to bind to human cells and tissues which helps spread the infection (2010 Hallstrom at al). | ||
== '''Structure''' == | |||
The two monomers (blue & green) are connected together at the C-terminus | |||
(purple) to form the dimer. The C-terminus is of significance because it was thought | |||
to be the binding site of the BbCRASP-1 protein because when the C-terminus | |||
(residues 241-250) was truncated, BbCRASP-1 was no longer able to bind to factor H | |||
(Cordes 2005). Through experimentation, it was suggested that the C-terminus is | |||
actually not the binding sight but a region that controls the structure of the protein. | |||
truncation of the C-terminus (241-250) causes the structure of the protein to change | |||
which causes factor H to not bind. To further test this, a buried leucine(residue 246) | |||
in the C-terminus (yellow) was mutated and replaced by aspartate. this also caused | |||
the protein to not bind to factor H. It was then concluded that the C-terminus is a | |||
structurally sensitive region rather than a direct binding site (cordes 2005). | |||
Revision as of 00:51, 5 May 2013
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 its immune system through the use of surface proteins. One of the proteins responsible for a successful initial infection is Borrelia burgdorferi complement regulator-acquiring surface protein 1, or BbCRASP-1 (....). Because BbCRASP-1 binds host complement regulators to the spirochete's outer surface, it remains undetected within the host (Bykowski et al. 2007). BbCRASP-1 specifically binds to complement Factor H (FH) and Factor H-like proteins (FHL-1), which are responsible for the host's immune response and detection of pathogens (Kraiczy et al. 2004).
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FunctionFunction
Bb CRASP-1 can be found on the outer layer of the Lyme disease spirochete and it is essential for the infiltration of the spirochete into the host (Bykowski 2007). BbCRASP-1 provides resistance for the spirochete against the hosts immune system. This is accomplished because BbCRASP-1 has an affinity for factor H and therefore, the spirochete is covered in factor H and able to infiltrate the host without being recognized (Bykowski 2007). Factor H is a complement control protein that can be found in plasma. It functions as a regulator that directs the complement system to pathogens so they don't harm the host (Alitalo 2002). BbCRASP-1 is biologically functional in its dimer form. If BbCRASP-1 isn't in the dimer form, it does not bind to Factor H ( Cordes 2005). More recently it was found that not only does Bb-CRASP bind to FH and FH like proteins, it also bind to several other human ligands such as BMP-2(bone morphogenetic protein 2) and Extra cellular matrix ligands Collagen I, Collagen III, Collagen IV, fibronectin, laminin, and plasminogen ( 2010 hallstrom at al.). As a result of this new finding, Bb-CRASP is said to advocate not only the bypassing of the complementary immune system, but the pathogenesis of lyme disease by facilitating “borrelia burgdoferi” to bind to human cells and tissues which helps spread the infection (2010 Hallstrom at al).
StructureStructure
The two monomers (blue & green) are connected together at the C-terminus (purple) to form the dimer. The C-terminus is of significance because it was thought to be the binding site of the BbCRASP-1 protein because when the C-terminus (residues 241-250) was truncated, BbCRASP-1 was no longer able to bind to factor H (Cordes 2005). Through experimentation, it was suggested that the C-terminus is actually not the binding sight but a region that controls the structure of the protein. truncation of the C-terminus (241-250) causes the structure of the protein to change which causes factor H to not bind. To further test this, a buried leucine(residue 246) in the C-terminus (yellow) was mutated and replaced by aspartate. this also caused the protein to not bind to factor H. It was then concluded that the C-terminus is a structurally sensitive region rather than a direct binding site (cordes 2005).