6npr
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of H-2Dd with C84-C139 disulfide in complex with gp120 derived peptide P18-I10== | |
| + | <StructureSection load='6npr' size='340' side='right'caption='[[6npr]], [[Resolution|resolution]] 2.37Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6npr]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NPR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6NPR 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=6npr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6npr OCA], [http://pdbe.org/6npr PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6npr RCSB], [http://www.ebi.ac.uk/pdbsum/6npr PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6npr 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/HA12_MOUSE HA12_MOUSE]] 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 == | ||
| + | The interplay between a highly polymorphic set of MHC-I alleles and molecular chaperones shapes the repertoire of peptide antigens displayed on the cell surface for T cell surveillance. Here, we demonstrate that the molecular chaperone TAP-binding protein related (TAPBPR) associates with a broad range of partially folded MHC-I species inside the cell. Bimolecular fluorescence complementation and deep mutational scanning reveal that TAPBPR recognition is polarized toward the alpha2 domain of the peptide-binding groove, and depends on the formation of a conserved MHC-I disulfide epitope in the alpha2 domain. Conversely, thermodynamic measurements of TAPBPR binding for a representative set of properly conformed, peptide-loaded molecules suggest a narrower MHC-I specificity range. Using solution NMR, we find that the extent of dynamics at "hotspot" surfaces confers TAPBPR recognition of a sparsely populated MHC-I state attained through a global conformational change. Consistently, restriction of MHC-I groove plasticity through the introduction of a disulfide bond between the alpha1/alpha2 helices abrogates TAPBPR binding, both in solution and on a cellular membrane, while intracellular binding is tolerant of many destabilizing MHC-I substitutions. Our data support parallel TAPBPR functions of 1) chaperoning unstable MHC-I molecules with broad allele-specificity at early stages of their folding process, and 2) editing the peptide cargo of properly conformed MHC-I molecules en route to the surface, which demonstrates a narrower specificity. Our results suggest that TAPBPR exploits localized structural adaptations, both near and distant to the peptide-binding groove, to selectively recognize discrete conformational states sampled by MHC-I alleles, toward editing the repertoire of displayed antigens. | ||
| - | + | Molecular determinants of chaperone interactions on MHC-I for folding and antigen repertoire selection.,McShan AC, Devlin CA, Overall SA, Park J, Toor JS, Moschidi D, Flores-Solis D, Choi H, Tripathi S, Procko E, Sgourakis NG Proc Natl Acad Sci U S A. 2019 Dec 17;116(51):25602-25613. doi:, 10.1073/pnas.1915562116. Epub 2019 Dec 3. PMID:31796585<ref>PMID:31796585</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: | + | <div class="pdbe-citations 6npr" style="background-color:#fffaf0;"></div> |
| - | [[Category: Sgourakis, N | + | == References == |
| - | + | <references/> | |
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: McShan, A C]] | ||
| + | [[Category: Sgourakis, N G]] | ||
[[Category: Toor, J]] | [[Category: Toor, J]] | ||
| + | [[Category: Tripathi, S M]] | ||
| + | [[Category: Antigen presentation]] | ||
| + | [[Category: Immune system]] | ||
| + | [[Category: Major histocompatibility complex]] | ||
Revision as of 16:11, 22 January 2020
Crystal structure of H-2Dd with C84-C139 disulfide in complex with gp120 derived peptide P18-I10
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