G18secL03Tpc4: Difference between revisions
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=== Major Hypothesized Functions === | === Major Hypothesized Functions === | ||
*Adaptation and survival in different host environments | *Adaptation and survival in different host environments | ||
''Borrelia burgdorferi'' expresses OspA but not OspC when residing in the midgut of unfed ticks. However, when the tick starts feeding on mammals, OspC synthesis is induced and OspA is repressed.The switch is in part due to the change in temperature; OspC is induced at 32–37°C, but not at 24°C, and this upregulation is at the transcriptional and translational levels. Evidence suggests co-regulation of these two genes at the mRNA level. Clearly, to survive in both hosts, spirochetes have evolved mechanisms for sensing the different host environments and responding accordingly.<ref | ''Borrelia burgdorferi'' expresses OspA but not OspC when residing in the midgut of unfed ticks. However, when the tick starts feeding on mammals, OspC synthesis is induced and OspA is repressed.The switch is in part due to the change in temperature; OspC is induced at 32–37°C, but not at 24°C, and this upregulation is at the transcriptional and translational levels. Evidence suggests co-regulation of these two genes at the mRNA level. Clearly, to survive in both hosts, spirochetes have evolved mechanisms for sensing the different host environments and responding accordingly.<ref name="Kum"/> | ||
*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 [http://en.wikipedia.org/wiki/Collagen collagenous] tissue and can interact with [http://en.wikipedia.org/wiki/Fibronectin fibronectin] and cellular collagens. The spirochetes can bind to a number of different cell types, including [http://en.wikipedia.org/wiki/Fibroblast 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 [http://en.wikipedia.org/wiki/Collagen collagenous] tissue and can interact with [http://en.wikipedia.org/wiki/Fibronectin fibronectin] and cellular collagens. The spirochetes can bind to a number of different cell types, including [http://en.wikipedia.org/wiki/Fibroblast 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=' ' scene='Insert optional scene name here' /> | <Structure load='1ggq' size='400' frame='true' align='right' caption=' ' 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. <scene name='G18secL03Tpc4/Binding_site_single_dimer/1'>Cavities</scene> 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 | 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. <scene name='G18secL03Tpc4/Binding_site_single_dimer/1'>Cavities</scene> 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 name="Kum"/> 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> | 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> | ||
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=== OspC-based Vaccine Against Lyme Disease === | === OspC-based Vaccine Against Lyme Disease === | ||
Researchers believe that an OspC based vaccine would be more effective against Lyme disease than the current OspA based vaccine once further research is conducted regarding the three dimensional structure of OspC's, especially the structure of invasive strains <ref | Researchers believe that an OspC based vaccine would be more effective against Lyme disease than the current OspA based vaccine once further research is conducted regarding the three dimensional structure of OspC's, especially the structure of invasive strains. <ref name="Kum"/> An OspC vaccine would have significant advantages over the current OspA vaccine, but there are several problems that require further research before the vaccine can be made. | ||
==== Main Advantages of Developing OspC-based Vaccine ==== | ==== Main Advantages of Developing OspC-based Vaccine ==== | ||
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=== Necessity of Further Research on OspC === | === Necessity of Further Research on OspC === | ||
The biological function of OspC is not yet completely understood. Further investigation is required to determine OspC ecology and its relatedness to the pathogenicity of ''B. Burgdorferi''. For the development of an effective OspC-based vaccine, it is important to know representative three-dimensional structures of at least a few more OspCs, especially those from the invasive strains. This information could be useful for rational design of an OspC-based recombinant vaccine.<ref | The biological function of OspC is not yet completely understood. Further investigation is required to determine OspC ecology and its relatedness to the pathogenicity of ''B. Burgdorferi''. For the development of an effective OspC-based vaccine, it is important to know representative three-dimensional structures of at least a few more OspCs, especially those from the invasive strains. This information could be useful for rational design of an OspC-based recombinant vaccine.<ref name="Kum"/> Also, further understanding of the evolution and genetics of Lyme Disease cause, ''Borrelia burgdorferi'', with its outer surface proteins such as OspC, fosters progress toward ecologically based control efforts.<ref>PMID:20877579</ref> | ||
=== 3D Structures === | === 3D Structures === | ||