G18secL03Tpc4: Difference between revisions
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A single OspC monomer subunit is composed of 4 long and 1 short α-helices. Also, 2 short segments of β-sheets are observed near the binding site of the molecule. | A single OspC monomer subunit is composed of 4 long and 1 short α-helices. Also, 2 short segments of β-sheets are observed near the binding site of the molecule. | ||
*Quaternary Structure | *Quaternary Structure | ||
OspC is a dimerized molecule, with 2 identical monomeric subunits comprising a dimer. However, for a binding event to occur, | OspC is a dimerized molecule, with 2 identical monomeric subunits comprising a dimer. However, for a binding event to occur, a tetramer made up of two dimers is necessary. | ||
=== Major Hypothesized Functions === | === Major Hypothesized Functions === | ||
*Adaptation and survival in different host environments | *Adaptation and survival in different host environments | ||
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*Binding and attachment to host's tissues | *Binding and attachment to host's tissues | ||
OspC may possibly be a binding protein contributing to a fundamental biological process and determining virulence of the bacteria. Several studies have shown that ''B.burgdorferi'' has a predilection for collagenous tissue and can interact with fibronectin and cellular collagens. The spirochetes can bind to a number of different cell types, including fibroblasts. ''Borrelia burgdorferi'' can bind to a novel circulating fibroblast-like cell called the peripheral blood fibrocyte, which expresses collagen types I and III as well as fibronectin, in a process that does not require OspA or OspB.<ref>PMID:10072447</ref> | OspC may possibly be a binding protein contributing to a fundamental biological process and determining virulence of the bacteria. Several studies have shown that ''B.burgdorferi'' has a predilection for collagenous tissue and can interact with fibronectin and cellular collagens. The spirochetes can bind to a number of different cell types, including fibroblasts. ''Borrelia burgdorferi'' can bind to a novel circulating fibroblast-like cell called the peripheral blood fibrocyte, which expresses collagen types I and III as well as fibronectin, in a process that does not require OspA or OspB.<ref>PMID:10072447</ref> | ||
==== Putative Binding Site ==== | ==== Putative Binding Site ==== | ||
<Structure load='1ggq' size='400' frame='true' align='right' caption='Insert caption here' scene='Insert optional scene name here' /> | <Structure load='1ggq' size='400' frame='true' align='right' caption='Insert caption here' scene='Insert optional scene name here' /> | ||
The <scene name='G18secL03Tpc4/Binding_site/1'>binding site</scene> of OspC is believed to be located on the surface that projects away from the membrane and has a region with strong negative electrostatic potential. Cavities are formed at the top of the molecule away from the membrane surface. Each cavity has a volume of 50 Å3 and is formed by residues Ala75, Ile76, Gly77, Lys78, Lys79, Glu89, Ala90, Asp91, His92 and Asn93 of one monomer, and Gly94, Ser95, Ser98, Gly146, Lys147 and Glu148 of the other monomer.<ref>D. Kumaran1, S. Eswaramoorthy1, B.J. Luft2, S. Koide3, J.J. Dunn1, C.L. Lawson1,4 and S. Swaminathan1. Crystal structure of outer surface protein C (OspC) from the Lyme disease spirochete, Borrelia burgdorferi.The EMBO Journal (2001) 20, 971 - 978 [http://dx.doi.org/DOI:10.1093/emboj/20.5.971]</ref> Positively charged Magnesium ion | The <scene name='G18secL03Tpc4/Binding_site/1'>binding site</scene> of OspC is believed to be located on the surface that projects away from the membrane and has a region with strong negative electrostatic potential. Cavities are formed at the top of the molecule away from the membrane surface. Each cavity has a volume of 50 Å3 and is formed by residues Ala75, Ile76, Gly77, Lys78, Lys79, Glu89, Ala90, Asp91, His92 and Asn93 of one monomer, and Gly94, Ser95, Ser98, Gly146, Lys147 and Glu148 of the other monomer.<ref>D. Kumaran1, S. Eswaramoorthy1, B.J. Luft2, S. Koide3, J.J. Dunn1, C.L. Lawson1,4 and S. Swaminathan1. Crystal structure of outer surface protein C (OspC) from the Lyme disease spirochete, Borrelia burgdorferi.The EMBO Journal (2001) 20, 971 - 978 [http://dx.doi.org/DOI:10.1093/emboj/20.5.971]</ref> Positively charged Magnesium ion | ||
<scene name='G18secL03Tpc4/Mg_ion/1'>Mg2+</scene> between the two dimers demonstrates the location of hypothesized binding site. | <scene name='G18secL03Tpc4/Mg_ion/1'>Mg2+</scene> between the two dimers demonstrates the location of hypothesized binding site. | ||
Fibronectin in humans, according to the study of its crystal structure, is positively charged, indicating a ligand to which the bacteria can bind through the use of OspC.<ref>PMID:10075919</ref> | |||
=== Role of OspC in Lyme Disease === | === Role of OspC in Lyme Disease === | ||
=== OspC-based Vaccine Against Lyme Disease === | === OspC-based Vaccine Against Lyme Disease === | ||