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4u1s
From Proteopedia
(Difference between revisions)
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| - | ''' | + | ==HLA class I micropolymorphisms determine peptide-HLA landscape and dictate differential HIV-1 escape through identical epitopes== |
| + | <StructureSection load='4u1s' size='340' side='right' caption='[[4u1s]], [[Resolution|resolution]] 1.76Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[4u1s]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4U1S OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4U1S FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | ||
| + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4u1h|4u1h]], [[4u1i|4u1i]], [[4u1j|4u1j]], [[4u1k|4u1k]], [[4u1l|4u1l]], [[4u1m|4u1m]], [[4u1n|4u1n]]</td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4u1s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4u1s OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4u1s RCSB], [http://www.ebi.ac.uk/pdbsum/4u1s PDBsum]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
| + | [[http://www.uniprot.org/uniprot/B2MG_HUMAN B2MG_HUMAN]] Defects in B2M are the cause of hypercatabolic hypoproteinemia (HYCATHYP) [MIM:[http://omim.org/entry/241600 241600]]. Affected individuals show marked reduction in serum concentrations of immunoglobulin and albumin, probably due to rapid degradation.<ref>PMID:16549777</ref> Note=Beta-2-microglobulin may adopt the fibrillar configuration of amyloid in certain pathologic states. The capacity to assemble into amyloid fibrils is concentration dependent. Persistently high beta(2)-microglobulin serum levels lead to amyloidosis in patients on long-term hemodialysis.<ref>PMID:3532124</ref> <ref>PMID:1336137</ref> <ref>PMID:7554280</ref> <ref>PMID:4586824</ref> <ref>PMID:8084451</ref> <ref>PMID:12119416</ref> <ref>PMID:12796775</ref> <ref>PMID:16901902</ref> <ref>PMID:16491088</ref> <ref>PMID:17646174</ref> <ref>PMID:18835253</ref> <ref>PMID:18395224</ref> <ref>PMID:19284997</ref> | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/1B81_HUMAN 1B81_HUMAN]] Involved in the presentation of foreign antigens to the immune system. [[http://www.uniprot.org/uniprot/B2MG_HUMAN B2MG_HUMAN]] Component of the class I major histocompatibility complex (MHC). Involved in the presentation of peptide antigens to the immune system. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | BACKGROUND: Presentation of identical HIV-1 peptides by closely related Human Leukocyte Antigen class I (HLAI) molecules can select distinct patterns of escape mutation that have a significant impact on viral fitness and disease progression. The molecular mechanisms by which HLAI micropolymorphisms can induce differential HIV-1 escape patterns within identical peptide epitopes remain unknown. RESULTS: Here, we undertook genetic and structural analyses of two immunodominant HIV-1 peptides, Gag180-188 (TPQDLNTML, TL9-p24) and Nef71-79 (RPQVPLRPM, RM9-Nef) that are among the most highly targeted epitopes in the global HIV-1 epidemic. We show that single polymorphisms between different alleles of the HLA-B7 superfamily can induce a conformational switch in peptide conformation that is associated with differential HLAI-specific escape mutation and immune control. A dominant R71K mutation in the Nef71-79 occurred in those with HLA-B*07:02 but not B*42:01/02 or B*81:01. No structural difference in the HLA-epitope complexes was detected to explain this observation. CONCLUSIONS: These data suggest that identical peptides presented through very similar HLAI landscapes are recognized as distinct epitopes and provide a novel structural mechanism for previously observed differential HIV-1 escape and disease progression. | ||
| - | + | A molecular switch in immunodominant HIV-1-specific CD8 T-cell epitopes shapes differential HLA-restricted escape.,Kloverpris HN, Cole DK, Fuller A, Carlson J, Beck K, Schauenburg AJ, Rizkallah PJ, Buus S, Sewell AK, Goulder P Retrovirology. 2015 Feb 20;12(1):20. doi: 10.1186/s12977-015-0149-5. PMID:25808313<ref>PMID:25808313</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | + | == References == | |
| - | + | <references/> | |
| - | [[Category: Cole, D | + | __TOC__ |
| - | + | </StructureSection> | |
| - | + | [[Category: Cole, D K]] | |
[[Category: Fuller, A]] | [[Category: Fuller, A]] | ||
| + | [[Category: Rizkallah, P J]] | ||
| + | [[Category: Sewell, A K]] | ||
| + | [[Category: Hiv]] | ||
| + | [[Category: Hla]] | ||
| + | [[Category: Immune system]] | ||
| + | [[Category: Immunoglobulin]] | ||
Revision as of 11:06, 8 April 2015
HLA class I micropolymorphisms determine peptide-HLA landscape and dictate differential HIV-1 escape through identical epitopes
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Categories: Cole, D K | Fuller, A | Rizkallah, P J | Sewell, A K | Hiv | Hla | Immune system | Immunoglobulin
