6npr

Crystal structure of H-2Dd with C84-C139 disulfide in complex with gp120 derived peptide P18-I10

spinqualitylabelsall models 6npr, resolution 2.37Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6npr is a 6 chain structure with sequence from Homo sapiens, Human immunodeficiency virus 1 and Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.37Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function HA12_MOUSE Involved in the presentation of foreign antigens to the immune system. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Beta-2 microglobulin 3D structures MHC 3D structures MHC I 3D structures

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