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5oqg
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of a single chain trimer composed of the MHC I heavy chain H-2Kb W167A, beta-2microglobulin, and and ovalbumin-derived peptide.== | |
| + | <StructureSection load='5oqg' size='340' side='right'caption='[[5oqg]], [[Resolution|resolution]] 1.90Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5oqg]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5OQG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5OQG 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]] 1.9Å</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=5oqg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5oqg OCA], [https://pdbe.org/5oqg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5oqg RCSB], [https://www.ebi.ac.uk/pdbsum/5oqg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5oqg ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/HA1B_MOUSE HA1B_MOUSE] Involved in the presentation of foreign antigens to the immune system.[https://www.uniprot.org/uniprot/B2MG_MOUSE B2MG_MOUSE] 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 == | ||
| + | Endoplasmic reticulum aminopeptidase 1 (ERAP1) and ERAP2 process N-terminally extended antigenic precursors for optimal loading onto major histocompatibility complex class I (MHC I) molecules. We and others have demonstrated that ERAP1 processes peptides bound to MHC I, but the underlying mechanism is unknown. To this end, we utilized single-chain trimers (SCT) of the ovalbumin-derived epitope SIINFEKL (SL8) tethered to the H2-Kb MHC I determinant from mouse and introduced three substitutions, E63A, K66A, and W167A, at the A-pocket of the peptide-binding groove in the MHC I heavy chain, which interact with the N termini of peptides. These variants significantly decreased SL8-presenting SCT at the cell surface in the presence of ERAP1, but did not affect overall SCT expression, indicating that ERAP1 trims the SL8 N terminus. Comparison of the X-ray crystal structures of WT and three variant SCTs revealed only minor perturbations of the peptide-binding domain in the variants. However, molecular dynamics simulations suggested that SL8 can dissociate partially within a sub-microsecond timescale, exposing its N terminus to the solvent. We also found that the C terminus of MHC I-bound SL8 remains deeply buried in the F-pocket of MHC I. Furthermore, free-energy calculations revealed that the three SCT variants exhibit lower free-energy barriers of N terminus dissociation than the WT Kb. Taken together, our results are consistent with a previously observed model in which the partial dissociation of bound peptides from MHC I exposes their N terminus to trimming by ERAP1, while their C terminus is anchored at the F-pocket. | ||
| - | + | The partial dissociation of MHC class I bound peptides exposes their N terminus to trimming by endoplasmic reticulum aminopeptidase 1.,Papakyriakou A, Reeves E, Beton M, Mikolajek H, Douglas L, Cooper G, Elliott T, Werner JM, James E J Biol Chem. 2018 Mar 29. pii: RA117.000313. doi: 10.1074/jbc.RA117.000313. PMID:29599287<ref>PMID:29599287</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 5oqg" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Mus musculus]] | ||
| + | [[Category: Mikolajek H]] | ||
| + | [[Category: Werner JM]] | ||
Current revision
Crystal structure of a single chain trimer composed of the MHC I heavy chain H-2Kb W167A, beta-2microglobulin, and and ovalbumin-derived peptide.
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