{"display":true,"structure":{"allele":{"alpha":{"identifier":"ipd-imgt:HLA34091","locus":"hla-a","match_type":"histo:exact","name":"HLA-A*68:01","slug":"hla_a_68_01","species_stem":"hla"},"beta":{}},"assemblies":{"1":{"assembly_name":"6pvc_1","chains":["A","B","G","H"],"downloaded_at":"2022-11-09T14:41:58.373492"}},"assembly_count":null,"assigned_chains":{"beta2m":{"chains":["B","D"],"match_type":"histo:assign_chains","score":0.99,"sequence":"MIQRTPKIQVYSRHPAENGKSNFLNCYVSGFHPSDIEVDLLKNGERIEKVEHSDLSFSKDWSFYLLYYTEFTPTEKDEYACRVNHVTLSQPKIVKWDRDM"},"mr1":{"chains":["A","C"],"match_type":"histo:assign_chains","score":1.0,"sequence":"MRTHSLRYFRLGVSDPIHGVPEFISVGYVDSHPITTYDSVTRQKEPRAPWMAENLAPDHWERYTQLLRGWQQMFKVELKRLQRHYNHSGSHTYQRMIGCELLEDGSTTGFLQYAYDGQDFLIFNKDTLSWLAVDNVAHTIKQAWEANQHELLYQKNWLEEECIAWLKRFLEYGKDTLQRTEPPLVRVNRKETFPGVTALFCKAHGFYPPEIYMTWMKNGEEIVQEIDYGDILPSGDGTYQAWASIELDPQSSNLYSCHVEHSGVHMVLQVP"},"tcr_alpha":{"chains":["E"],"match_type":"stcrdab","sequence":"MGQNIDQPTEMTATEGAIVQINCTYQTSGFNGLFWYQQHAGEAPTFLSYNVLDGLEEKGRFSSFLSRSKGYSYLLLKELQMKDSASYLCAVKDSNYQLIWGAGTKLIIKPDIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESS","subgroup":"TRAV1"},"tcr_beta":{"chains":["F"],"match_type":"stcrdab","sequence":"MNAGVTQTPKFQVLKTGQSMTLQCAQDMNHNSMYWYRQDPGMGLRLIYYSASEGTTDKGEVPNGYNVSRLNKREFSLRLESAAPSQTSVYFCASSVWTGEGSGELFFGEGSRLTVLEDLKNVFPPEVAVFEPSEAEISHTQKATLVCLATGFYPDHVELSWWVNGKEVHSGVCTDPQPLKEQPALNDSRYALSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRAD","subgroup":"TRBV6"}},"chronology":{"deposition_date":"2019-07-20","deposition_year":2019,"release_date":"2020-04-01","release_year":2020,"revision_date":"2020-05-27","revision_year":2020},"class":"class_i","classical":false,"complex_type":"mr1_with_alpha_beta_tcr","components":["mr1","beta2m","tcr_alpha","tcr_beta"],"experimental_method":"X-ray diffraction","facets":{},"ligands":[],"locus":"hla-a","manually_edited":{},"missing_residues":[],"page_title":"6PVC | Non-classical MHC Class I molecule MR1 with Alpha/Beta T cell receptor","pdb_code":"6pvc","pdb_title":"Structure of human MAIT a-f7 TCR in complex with human MR1-db28","peptide":{"actual_sequence":null,"epitope_info":{},"features":[],"full_sequence":null,"gap_info":{},"gapped_sequence":null,"length":{"numeric":null,"text":null},"unnatural_amino_acids":[]},"publication":{"abstract":"The antigen-presenting molecule MR1 presents riboflavin-based metabolites to Mucosal-Associated Invariant T (MAIT) cells. While MR1 egress to the cell surface is ligand-dependent, the ability of small-molecule ligands to impact on MR1 cellular trafficking remains unknown. Arising from an in silico screen of the MR1 ligand-binding pocket, we identify one ligand, 3-([2,6-dioxo-1,2,3,6-tetrahydropyrimidin-4-yl]formamido)propanoic acid, DB28, as well as an analog, methyl 3-([2,6-dioxo-1,2,3,6-tetrahydropyrimidin-4-yl]formamido)propanoate, NV18.1, that down-regulate MR1 from the cell surface and retain MR1 molecules in the endoplasmic reticulum (ER) in an immature form. DB28 and NV18.1 compete with the known MR1 ligands, 5-OP-RU and acetyl-6-FP, for MR1 binding and inhibit MR1-dependent MAIT cell activation. Crystal structures of the MAIT T cell receptor (TCR) complexed with MR1-DB28 and MR1-NV18.1, show that these two ligands reside within the A'-pocket of MR1. Neither ligand forms a Schiff base with MR1 molecules; both are nevertheless sequestered by a network of hydrophobic and polar contacts. Accordingly, we define a class of compounds that inhibits MR1 cellular trafficking.","bibjson":{"author":[{"initials":"M","lastname":"Salio","name":"Salio M"},{"initials":"W","lastname":"Awad","name":"Awad W"},{"initials":"N","lastname":"Veerapen","name":"Veerapen N"},{"initials":"C","lastname":"Gonzalez-Lopez","name":"Gonzalez-Lopez C"},{"initials":"C","lastname":"Kulicke","name":"Kulicke C"},{"initials":"D","lastname":"Waithe","name":"Waithe D"},{"initials":"AWJ","lastname":"Martens","name":"Martens AWJ"},{"initials":"DM","lastname":"Lewinsohn","name":"Lewinsohn DM"},{"initials":"JV","lastname":"Hobrath","name":"Hobrath JV"},{"initials":"LR","lastname":"Cox","name":"Cox LR"},{"initials":"J","lastname":"Rossjohn","name":"Rossjohn J"},{"initials":"GS","lastname":"Besra","name":"Besra GS"},{"initials":"V","lastname":"Cerundolo","name":"Cerundolo V"}],"identifier":[{"id":"10.1073/pnas.2003136117","type":"doi"},{"id":"32341160","type":"pubmed"}],"issue":[null],"journal":{"iso_abbreviation":"Proc. Natl. Acad. Sci. U.S.A.","name":""},"pages":[null],"title":"Ligand-dependent downregulation of MR1 cell surface expression.","type":"article","url":"https://pnas.org/doi/full/10.1073/pnas.2003136117","volume":[null],"year":[2020]},"in_pmc":"N","in_pmce":"Y","open_access":"Y"},"resolution":"1.96","same_as":{"pdbe":{"url":"https://www.ebi.ac.uk/pdbe/entry/pdb/6pvc"},"rcsb":{"url":"https://www.rcsb.org/structure/6pvc"},"stcrdab":{"url":"http://opig.stats.ox.ac.uk/webapps/stcrdab/StrViewer?pdb=6pvc"}},"species":{"common_name":"Human","match_type":"histo:assign_species","scientific_name":"Homo sapiens","slug":"homo_sapiens"},"tcr":{"alpha":{"chains":["E"],"subgroup":"TRAV1"},"beta":{"chains":["F"],"subgroup":"TRBV6"},"pdb_code":"6pvc"},"title":"Non-classical MHC Class I molecule MR1 with Alpha/Beta T cell receptor at 1.96Å resolution","unique_chain_count":4}}