3vri

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[[Image:3vri.jpg|left|200px]]
 
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==HLA-B*57:01-RVAQLENVYI in complex with abacavir==
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The line below this paragraph, containing "STRUCTURE_3vri", creates the "Structure Box" on the page.
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<StructureSection load='3vri' size='340' side='right'caption='[[3vri]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[3vri]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3VRI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3VRI FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.6&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1KX:{(1S,4R)-4-[2-AMINO-6-(CYCLOPROPYLAMINO)-9H-PURIN-9-YL]CYCLOPENT-2-EN-1-YL}METHANOL'>1KX</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
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{{STRUCTURE_3vri| PDB=3vri | SCENE= }}
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3vri FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vri OCA], [https://pdbe.org/3vri PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3vri RCSB], [https://www.ebi.ac.uk/pdbsum/3vri PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3vri ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/B2MG_HUMAN B2MG_HUMAN] Defects in B2M are the cause of hypercatabolic hypoproteinemia (HYCATHYP) [MIM:[https://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>
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== Function ==
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[https://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.
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Human leukocyte antigens (HLAs) are highly polymorphic proteins that initiate immunity by presenting pathogen-derived peptides to T cells. HLA polymorphisms mostly map to the antigen-binding cleft, thereby diversifying the repertoire of self-derived and pathogen-derived peptide antigens selected by different HLA allotypes. A growing number of immunologically based drug reactions, including abacavir hypersensitivity syndrome (AHS) and carbamazepine-induced Stevens-Johnson syndrome (SJS), are associated with specific HLA alleles. However, little is known about the underlying mechanisms of these associations, including AHS, a prototypical HLA-associated drug reaction occurring exclusively in individuals with the common histocompatibility allele HLA-B*57:01, and with a relative risk of more than 1,000 (refs 6, 7). We show that unmodified abacavir binds non-covalently to HLA-B*57:01, lying across the bottom of the antigen-binding cleft and reaching into the F-pocket, where a carboxy-terminal tryptophan typically anchors peptides bound to HLA-B*57:01. Abacavir binds with exquisite specificity to HLA-B*57:01, changing the shape and chemistry of the antigen-binding cleft, thereby altering the repertoire of endogenous peptides that can bind HLA-B*57:01. In this way, abacavir guides the selection of new endogenous peptides, inducing a marked alteration in 'immunological self'. The resultant peptide-centric 'altered self' activates abacavir-specific T-cells, thereby driving polyclonal CD8 T-cell activation and a systemic reaction manifesting as AHS. We also show that carbamazepine, a widely used anti-epileptic drug associated with hypersensitivity reactions in HLA-B*15:02 individuals, binds to this allotype, producing alterations in the repertoire of presented self peptides. Our findings simultaneously highlight the importance of HLA polymorphism in the evolution of pharmacogenomics and provide a general mechanism for some of the growing number of HLA-linked hypersensitivities that involve small-molecule drugs.
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===HLA-B*57:01-RVAQLENVYI in complex with abacavir===
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Immune self-reactivity triggered by drug-modified HLA-peptide repertoire.,Illing PT, Vivian JP, Dudek NL, Kostenko L, Chen Z, Bharadwaj M, Miles JJ, Kjer-Nielsen L, Gras S, Williamson NA, Burrows SR, Purcell AW, Rossjohn J, McCluskey J Nature. 2012 Jun 28;486(7404):554-8. PMID:22722860<ref>PMID:22722860</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 3vri" style="background-color:#fffaf0;"></div>
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==About this Structure==
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==See Also==
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[[3vri]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3VRI OCA].
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*[[Beta-2 microglobulin 3D structures|Beta-2 microglobulin 3D structures]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Illing, P T.]]
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[[Category: Large Structures]]
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[[Category: McCluskey, J.]]
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[[Category: Illing PT]]
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[[Category: Rossjohn, J.]]
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[[Category: McCluskey J]]
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[[Category: Vivian, J P.]]
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[[Category: Rossjohn J]]
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[[Category: Antigen presentation]]
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[[Category: Vivian JP]]
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[[Category: Human leukocyte antigen]]
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[[Category: Immune system]]
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[[Category: T-cell receptor]]
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Current revision

HLA-B*57:01-RVAQLENVYI in complex with abacavir

PDB ID 3vri

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