StudioG24SecL04Tpc5: Difference between revisions
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===Variable Region=== | ===Variable Region=== | ||
The outer surface lipoprotein of ''Borrelia burgdorferi'' uses antigenic variation via gene conversion to evade host immune response. Crystal structure of VlsE1, a recombinant variant protein of VlsE, reveals six <scene name='StudioG24SecL04Tpc5/Variable_region/2'>variable regions</scene> that form loop structures that entirely cover the membrane distal end of the protein. <ref>PMID: 11923306</ref> Almost 50% of the variable region’s surface area is exposed on the surface of | The outer surface lipoprotein of ''Borrelia burgdorferi'' uses antigenic variation via gene conversion to evade host immune response. Crystal structure of VlsE1, a recombinant variant protein of VlsE, reveals six <scene name='StudioG24SecL04Tpc5/Variable_region/2'>variable regions</scene> that form loop structures that entirely cover the membrane distal end of the protein. <ref>PMID: 11923306</ref> Almost 50% of the variable region’s surface area is exposed on the surface of | ||
<scene name='StudioG24SecL04Tpc5/Vlse_cassete_region_highlight/1'>VlsE</scene>. There are three major areas of the membrane distal portion on the protein surface that undergo [http://en.wikipedia.org/wiki/Antigenic_variation antigenic variation]<br> | <scene name='StudioG24SecL04Tpc5/Vlse_cassete_region_highlight/1'>VlsE</scene>. There are three major areas of the membrane distal portion on the protein surface that undergo [http://en.wikipedia.org/wiki/Antigenic_variation antigenic variation.]<br><ref>PMID: 11923306</ref>It is likely that amino acid mutations of these residues change conformation of the looped structures and therefore vary the [http://en.wikipedia.org/wiki/Epitope epitope]<br>throughout each variable region. Immune systems are overwhelmed with an astronomical number of different antigens. The loop structures cover predominantly the α-helical invariant regions of the protein. <ref>PMID: 11923306</ref> It is speculated that the locations of these variable regions on the membrane distal end shield the conserved regions of VlsE from antibody interaction and thereby contribute to immune evasion. <ref>PMID: 11923306</ref> | ||
In the experimental infection of mice, segments of the silent cassette recombines via gene conversion mechanism into the ''vlsE'' cassette region. The changes in sequence were detected after 4 days after experimental infection in mice. 28 days later, every skin isolate and other tissues were unique in that they contained about 9-13 recombination events. It is hypothesized that the humoral immune response cannot cope to a seemingly continuous generation of VlsE variants. This permits immune evasion and persistent infection.<ref>PMID: 11923306</ref> | |||
===Invariable=== | ===Invariable=== | ||
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==Function in Immune System Evasion== | ==Function in Immune System Evasion== | ||
The contributions that VlsE brings to immune evasion of Lyme Disease in B. Burgderfori is brought on by the property of antigenic variation. The variable domain of VlsE keeps the immune system guessing by constantly changing its side chains. The predicted amount of variations due to VlsE sequence is around 10^30 combinations providing ample evasion against immune responses. The variable region also protects the invariable region by covering the latter region, providing antibodies with a small area to attach to the antigen. There are only 4 amino residues on IR6 that are exposed on the surface of the protein and allowed for binding by antibody. They are Lysine-276, Glutamine-279, Lysine-291, and Lysine-294. The IR6 region exposed is only 13.7% of the entire surface area of VlsE, making immune evasion even easier.<ref name="A">PMID:10569796</ref> | The contributions that VlsE brings to immune evasion of Lyme Disease in B. Burgderfori is brought on by the property of antigenic variation. The variable domain of VlsE keeps the immune system guessing by constantly changing its side chains. The predicted amount of variations due to VlsE sequence is around 10^30 combinations providing ample evasion against immune responses. The variable region also protects the invariable region by covering the latter region, providing antibodies with a small area to attach to the antigen. There are only 4 amino residues on IR6 that are exposed on the surface of the protein and allowed for binding by antibody. They are Lysine-276, Glutamine-279, Lysine-291, and Lysine-294. The IR6 region exposed is only 13.7% of the entire surface area of VlsE, making immune evasion even easier.<ref name="A">PMID:10569796</ref> | ||
<scene name='StudioG24SecL04Tpc5/The_resudie/2'>Exposed Residues of IR6 highlighted in blue</scene> | |||
==Clinical Application== | ==Clinical Application== | ||
