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| | ==Crystal Structure of a disulfide trapped single chain trimer composed of the MHC I heavy chain H-2Kb Y84C E63A mutant, beta-2microglobulin, and ovalbumin-derived peptide== | | ==Crystal Structure of a disulfide trapped single chain trimer composed of the MHC I heavy chain H-2Kb Y84C E63A mutant, beta-2microglobulin, and ovalbumin-derived peptide== |
| - | <StructureSection load='5oqi' size='340' side='right' caption='[[5oqi]], [[Resolution|resolution]] 2.40Å' scene=''> | + | <StructureSection load='5oqi' size='340' side='right'caption='[[5oqi]], [[Resolution|resolution]] 2.40Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5oqi]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5OQI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5OQI FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5oqi]] 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=5OQI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5OQI FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">H2-K1, H2-K ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4Å</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=5oqi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5oqi OCA], [http://pdbe.org/5oqi PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5oqi RCSB], [http://www.ebi.ac.uk/pdbsum/5oqi PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5oqi ProSAT]</span></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=5oqi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5oqi OCA], [https://pdbe.org/5oqi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5oqi RCSB], [https://www.ebi.ac.uk/pdbsum/5oqi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5oqi ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://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. | + | [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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Large Structures]] |
| - | [[Category: Beton, M E]] | + | [[Category: Mus musculus]] |
| - | [[Category: Mikolajek, H]] | + | [[Category: Beton ME]] |
| - | [[Category: Werner, J M]] | + | [[Category: Mikolajek H]] |
| - | [[Category: Antigen]] | + | [[Category: Werner JM]] |
| - | [[Category: Diagnosis]]
| + | |
| - | [[Category: Epitope]]
| + | |
| - | [[Category: Immune system]]
| + | |
| - | [[Category: Major histocompatibility complex]]
| + | |
| - | [[Category: Mice]]
| + | |
| - | [[Category: Model]]
| + | |
| - | [[Category: Molecular]]
| + | |
| - | [[Category: Molecular conformation]]
| + | |
| - | [[Category: Peptide]]
| + | |
| - | [[Category: Receptor]]
| + | |
| - | [[Category: T-cell]]
| + | |
| - | [[Category: T-lymphocyte]]
| + | |
| - | [[Category: Vaccine]]
| + | |
| Structural highlights
Function
HA1B_MOUSE Involved in the presentation of foreign antigens to the immune system.B2MG_MOUSE Component of the class I major histocompatibility complex (MHC). Involved in the presentation of peptide antigens to the immune system.
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Papakyriakou A, Reeves E, Beton M, Mikolajek H, Douglas L, Cooper G, Elliott T, Werner JM, James E. The partial dissociation of MHC class I bound peptides exposes their N terminus to trimming by endoplasmic reticulum aminopeptidase 1. J Biol Chem. 2018 Mar 29. pii: RA117.000313. doi: 10.1074/jbc.RA117.000313. PMID:29599287 doi:http://dx.doi.org/10.1074/jbc.RA117.000313
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