VlsE: Difference between revisions
From Proteopedia
Jump to navigationJump to search
Michal Harel (talk | contribs) No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
<StructureSection load='1l8w' size='400' side='right' scene='' caption='VlsE lipoprotein tetramer [[1l8w]]'> | |||
[[Image:1L8W_2_pdb.jpg|thumb|300px|alt=text|VlsE]] | [[Image:1L8W_2_pdb.jpg|thumb|300px|alt=text|VlsE]] | ||
==Introduction== | ==Introduction== | ||
| Line 8: | Line 9: | ||
==Structural Overview== | ==Structural Overview== | ||
VlsE is a tetramer that consists of four identical subunits: <scene name='G21SecL01Tpc5/Chain_a/1'>chains A</scene>, B, C, and D. Making up the protein are two invariable regions, found at the N and C terminal regions, and one central variable domain <ref>PMID: 11923306</ref><ref>PMID: 10569796</ref>. Within the variable domain are six variable (VR) and six invariable regions (IR). Since the N and C terminal regions do not go through constant changes, it was thought they would make great targets for antibodies to attach to. But due to the tightly packed structure of the VlsE and its lateral surface areas binding to other proteins, the terminal regions did not react well with the antibodies. This resulted in low levels of antibody attachment to the surface of the VlsE. Instead, a region within the VlsE that is protected by the antigenic variable system, known as IR6, was found to be the most reactive towards antibodies. | VlsE is a tetramer that consists of four identical subunits: <scene name='G21SecL01Tpc5/Chain_a/1'>chains A</scene>, B, C, and D. Making up the protein are two invariable regions, found at the N and C terminal regions, and one central variable domain <ref>PMID: 11923306</ref><ref>PMID: 10569796</ref>. Within the variable domain are six variable (VR) and six invariable regions (IR). Since the N and C terminal regions do not go through constant changes, it was thought they would make great targets for antibodies to attach to. But due to the tightly packed structure of the VlsE and its lateral surface areas binding to other proteins, the terminal regions did not react well with the antibodies. This resulted in low levels of antibody attachment to the surface of the VlsE. Instead, a region within the VlsE that is protected by the antigenic variable system, known as IR6, was found to be the most reactive towards antibodies. | ||
| Line 29: | Line 28: | ||
==Diagnostic Testing== | ==Diagnostic Testing== | ||
< | <scene name='G21SecL01Tpc5/A-helix_10/4'>VlsE IR6</scene> | ||
Lyme disease presents with symptoms of [http://onlinelibrary.wiley.com/doi/10.1111/j.1749-6632.1988.tb31834.x/abstract erythema migrans (EM)], arthritis, heart disease, and neurologic abnormalities. If not treated early these symptoms can cause permanent damage to the relative tissues. Using antibiotics, Lyme Disease can be treat and usually cured; however it is hard to diagnose early on and usually goes unnoticed until irreversible symptoms arise. Though, VlsE's function is not known it can be used to diagnose Lyme Disease through invariable region-6. Invariable region-6 (IR6) is important for diagnosis because it is highly reactive to antibody interaction. Although, IR6 has only 13.7% of its surface visible to antibody interactions this is the only site capable for use in human diagnostics.<ref>PMID:11923306</ref> Contained in alpha helix 10 it is composed of 26 peptides, four of which establish antibody adhesion. Amino acids <scene name='G21SecL01Tpc5/Lys-276_and_gln-279/5'>Lys-276(Green), Gln-279(Purple)</scene>, <scene name='G21SecL01Tpc5/Lys-276_and_gln-279/9'>Lys-291, and Lys-295</scene> all contain polar regions that branch out into the extra cellular space. Unlike most residues Lys and Gln side chains can perform a wider range of movements to establish better kinetics with paratopes, permitting higher affinity. Recently these regions have been the target for serodiagnosis using immunoassays. In order to do this, Human blood serum is mixed with detergent to lyse the protein and expose IR6. [http://www.ncbi.nlm.nih.gov/pubmed/11023468 Western blot and ELISA] assays are then used to determine the presents of the pathogen.<ref>PMID:21778118</ref> Depending on the results one or more tests are performed to establish an accurate measure. This procedure is highly expensive nevertheless and is usually performed on patients within Ixode tick infested areas. | Lyme disease presents with symptoms of [http://onlinelibrary.wiley.com/doi/10.1111/j.1749-6632.1988.tb31834.x/abstract erythema migrans (EM)], arthritis, heart disease, and neurologic abnormalities. If not treated early these symptoms can cause permanent damage to the relative tissues. Using antibiotics, Lyme Disease can be treat and usually cured; however it is hard to diagnose early on and usually goes unnoticed until irreversible symptoms arise. Though, VlsE's function is not known it can be used to diagnose Lyme Disease through invariable region-6. Invariable region-6 (IR6) is important for diagnosis because it is highly reactive to antibody interaction. Although, IR6 has only 13.7% of its surface visible to antibody interactions this is the only site capable for use in human diagnostics.<ref>PMID:11923306</ref> Contained in alpha helix 10 it is composed of 26 peptides, four of which establish antibody adhesion. Amino acids <scene name='G21SecL01Tpc5/Lys-276_and_gln-279/5'>Lys-276(Green), Gln-279(Purple)</scene>, <scene name='G21SecL01Tpc5/Lys-276_and_gln-279/9'>Lys-291, and Lys-295</scene> all contain polar regions that branch out into the extra cellular space. Unlike most residues Lys and Gln side chains can perform a wider range of movements to establish better kinetics with paratopes, permitting higher affinity. Recently these regions have been the target for serodiagnosis using immunoassays. In order to do this, Human blood serum is mixed with detergent to lyse the protein and expose IR6. [http://www.ncbi.nlm.nih.gov/pubmed/11023468 Western blot and ELISA] assays are then used to determine the presents of the pathogen.<ref>PMID:21778118</ref> Depending on the results one or more tests are performed to establish an accurate measure. This procedure is highly expensive nevertheless and is usually performed on patients within Ixode tick infested areas. | ||
</StructureSection> | |||
__NOTOC__ | |||
==Notes== | ==Notes== | ||
