View source for 6npr


==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]] 2.37&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6npr]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens], [https://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. 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 [https://proteopedia.org/fgij/fg.htm?mol=6NPR 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]] 2.37&#8491;</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=6npr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6npr OCA], [https://pdbe.org/6npr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6npr RCSB], [https://www.ebi.ac.uk/pdbsum/6npr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6npr ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/HA12_MOUSE HA12_MOUSE] Involved in the presentation of foreign 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&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 6npr" style="background-color:#fffaf0;"></div>

==See Also==
*[[Beta-2 microglobulin 3D structures|Beta-2 microglobulin 3D structures]]
*[[MHC 3D structures|MHC 3D structures]]
*[[MHC I 3D structures|MHC I 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Human immunodeficiency virus 1]]
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: McShan AC]]
[[Category: Sgourakis NG]]
[[Category: Toor J]]
[[Category: Tripathi SM]]