3qfd
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| - | {{STRUCTURE_3qfd| PDB=3qfd | SCENE= }} | ||
| - | ===Human Class I MHC HLA-A2 in complex with Mart-1(27-35) nonameric peptide=== | ||
| - | {{ABSTRACT_PUBMED_21937447}} | ||
| - | == | + | ==Human Class I MHC HLA-A2 in complex with Mart-1(27-35) nonameric peptide== |
| - | [[http://www.uniprot.org/uniprot/B2MG_HUMAN B2MG_HUMAN | + | <StructureSection load='3qfd' size='340' side='right'caption='[[3qfd]], [[Resolution|resolution]] 1.68Å' scene=''> |
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[3qfd]] is a 6 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=3QFD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3QFD FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.68Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3qfd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qfd OCA], [https://pdbe.org/3qfd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3qfd RCSB], [https://www.ebi.ac.uk/pdbsum/3qfd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3qfd ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
| + | [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> | ||
| + | == Function == | ||
| + | [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. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Modification of the primary anchor positions of antigenic peptides to improve binding to major histocompatibility complex (MHC) proteins is a commonly used strategy for engineering peptide-based vaccine candidates. Yet such peptide modifications do not always improve antigenicity, complicating efforts to design effective vaccines for cancer and infectious disease. Here we investigated the MART-127-35 tumor antigen, for which anchor modification (replacement of the position two alanine with leucine) dramatically reduces or ablates antigenicity with a wide range of T cell clones, despite significantly improving peptide binding to MHC. We found that anchor modification in the MART-1(27-35) antigen enhances the flexibility of both the peptide and the HLA-A*0201 molecule. Although the resulting entropic effects contribute to the improved binding of the peptide to MHC, they will also negatively impact TCR binding to the peptide/MHC complex. These results help explain how the "anchor fixing" strategy fails to improve antigenicity in this case, and, more generally, may be relevant for understanding elements of the high specificity characteristic of the T cell repertoire. In addition to impacting vaccine design, modulation of peptide and MHC flexibility through changes to antigenic peptides may present an evolutionary strategy for the escape of pathogens from immune destruction. | ||
| - | + | Loss of T cell antigen recognition arising from changes in peptide and major histocompatibility complex protein flexibility: implications for vaccine design.,Insaidoo F, Borbulevych OY, Hossain M, Santhanagopolan SM, Baxter TK, Baker BM J Biol Chem. 2011 Sep 21. PMID:21937447<ref>PMID:21937447</ref> | |
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| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| + | <div class="pdbe-citations 3qfd" style="background-color:#fffaf0;"></div> | ||
==See Also== | ==See Also== | ||
| - | *[[Beta-2 microglobulin|Beta-2 microglobulin]] | + | *[[Beta-2 microglobulin 3D structures|Beta-2 microglobulin 3D structures]] |
| - | + | == References == | |
| - | == | + | <references/> |
| - | + | __TOC__ | |
| + | </StructureSection> | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
| - | [[Category: | + | [[Category: Large Structures]] |
| - | [[Category: | + | [[Category: Baker BM]] |
| - | [[Category: | + | [[Category: Borbulevych OY]] |
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Current revision
Human Class I MHC HLA-A2 in complex with Mart-1(27-35) nonameric peptide
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