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However, the exact molecular bases underlying peptide selection and binding by MHC-I remain largely unknown. Within the peptide-loading complex, the peptide editor tapasin is key to the selection of MHC-I-bound peptides. Here, we have determined an ensemble of crystal structures of MHC-I in complex with the peptide exchange-associated dipeptide GL, as well as the tapasin-associated scoop loop, alone or in combination with candidate epitopes. These results combined with mutation analyses allow us to propose a molecular model underlying MHC-I peptide selection by tapasin. The N termini of bound peptides most probably bind first in the N-terminal and middle region of the MHC-I peptide binding cleft, upon which the peptide C termini are tested for their capacity to dislodge the tapasin scoop loop from the F pocket of the MHC-I cleft. Our results also indicate important differences in peptide selection between different MHC-I alleles.","bibjson":{"author":[{"initials":"I","lastname":"Hafstrand","name":"Hafstrand I"},{"initials":"EC","lastname":"Sayitoglu","name":"Sayitoglu EC"},{"initials":"A","lastname":"Apavaloaei","name":"Apavaloaei A"},{"initials":"BJ","lastname":"Josey","name":"Josey BJ"},{"initials":"R","lastname":"Sun","name":"Sun R"},{"initials":"X","lastname":"Han","name":"Han X"},{"initials":"S","lastname":"Pellegrino","name":"Pellegrino S"},{"initials":"D","lastname":"Ozkazanc","name":"Ozkazanc D"},{"initials":"R","lastname":"Potens","name":"Potens R"},{"initials":"L","lastname":"Janssen","name":"Janssen L"},{"initials":"J","lastname":"Nilvebrant","name":"Nilvebrant J"},{"initials":"P\u00c5","lastname":"Nygren","name":"Nygren P\u00c5"},{"initials":"T","lastname":"Sandalova","name":"Sandalova T"},{"initials":"S","lastname":"Springer","name":"Springer S"},{"initials":"AM","lastname":"Georgoudaki","name":"Georgoudaki AM"},{"initials":"AD","lastname":"Duru","name":"Duru AD"},{"initials":"A","lastname":"Achour","name":"Achour A"}],"identifier":[{"id":"10.1073/pnas.1807656116","type":"doi"},{"id":"30808808","type":"pubmed"}],"issue":[null],"journal":{"iso_abbreviation":"Proc. Natl. Acad. Sci. U.S.A.","name":""},"pages":[null],"title":"Successive crystal structure snapshots suggest the basis for MHC class I peptide loading and editing by tapasin.","type":"article","url":"https://pnas.org/doi/full/10.1073/pnas.1807656116","volume":[null],"year":[2019]},"in_pmc":"N","in_pmce":"Y","open_access":"N"},"resolution":"1.78","same_as":{"pdbe":{"url":"https://www.ebi.ac.uk/pdbe/entry/pdb/6gb6"},"rcsb":{"url":"https://www.rcsb.org/structure/6gb6"}},"species":{"common_name":"Mouse","match_type":"histo:assign_species","scientific_name":"Mus musculus","slug":"mus_musculus"},"tcr":null,"title":"H2-Kb possibly without \"peptide\" at 1.78&#8491; resolution","unique_chain_count":2}}