5jzi
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of 1406 TCR bound to HLA-A2 with HCV 1406-1415 antigen peptide== | |
| + | <StructureSection load='5jzi' size='340' side='right' caption='[[5jzi]], [[Resolution|resolution]] 2.50Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5jzi]] is a 10 chain structure. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=4zez 4zez]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5JZI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5JZI FirstGlance]. <br> | ||
| + | </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=5jzi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5jzi OCA], [http://pdbe.org/5jzi PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5jzi RCSB], [http://www.ebi.ac.uk/pdbsum/5jzi PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5jzi ProSAT]</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/1A02_HUMAN 1A02_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 == | ||
| + | T-cell receptor (TCR) allorecognition is often presumed to be relatively nonspecific, attributable to either a TCR focus on exposed major histocompatibility complex (MHC) polymorphisms or the degenerate recognition of allopeptides. However, paradoxically, alloreactivity can proceed with high peptide and MHC specificity. Although the underlying mechanisms remain unclear, the existence of highly specific alloreactive TCRs has led to their use as immunotherapeutics that can circumvent central tolerance and limit graft-versus-host disease. Here, we show how an alloreactive TCR achieves peptide and MHC specificity. The HCV1406 TCR was cloned from T cells that expanded when a hepatitis C virus (HCV)-infected HLA-A2- individual received an HLA-A2+ liver allograft. HCV1406 was subsequently shown to recognize the HCV nonstructural protein 3 (NS3):1406-1415 epitope with high specificity when presented by HLA-A2. We show that NS3/HLA-A2 recognition by the HCV1406 TCR is critically dependent on features unique to both the allo-MHC and the NS3 epitope. We also find cooperativity between structural mimicry and a crucial peptide "hot spot" and demonstrate its role, along with the MHC, in directing the specificity of allorecognition. Our results help explain the paradox of specificity in alloreactive TCRs and have implications for their use in immunotherapy and related efforts to manipulate TCR recognition, as well as alloreactivity in general. | ||
| - | + | How an alloreactive T-cell receptor achieves peptide and MHC specificity.,Wang Y, Singh NK, Spear TT, Hellman LM, Piepenbrink KH, McMahan RH, Rosen HR, Vander Kooi CW, Nishimura MI, Baker BM Proc Natl Acad Sci U S A. 2017 Jun 13;114(24):E4792-E4801. doi:, 10.1073/pnas.1700459114. Epub 2017 Jun 1. PMID:28572406<ref>PMID:28572406</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 5jzi" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Baker, B M]] | ||
| + | [[Category: Piepenbrink, K H]] | ||
[[Category: Wang, Y]] | [[Category: Wang, Y]] | ||
| - | [[Category: | + | [[Category: Decapeptide]] |
| - | [[Category: | + | [[Category: Hcv ns3:1406-1415 peptide]] |
| + | [[Category: Hcv1406 tcr]] | ||
| + | [[Category: Hla-a2]] | ||
| + | [[Category: Immune system complex]] | ||
| + | [[Category: Protein binding]] | ||
| + | [[Category: Protein binding-immune system complex]] | ||
Revision as of 09:02, 3 August 2017
Crystal structure of 1406 TCR bound to HLA-A2 with HCV 1406-1415 antigen peptide
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