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covalent conjugation of a 14-carbon saturated fatty acid (myristic acid) to the amino-terminal glycine residue is critical for some viral proteins to function. This protein lipidation modification, termed N-myristoylation, is targeted by host cytotoxic T lymphocytes (CTLs) that specifically recognize N-myristoylated short peptides; however, the molecular mechanisms underlying lipopeptide antigen (Ag) presentation remain elusive. Here we show that a primate major histocompatibility complex (MHC) class I-encoded protein is capable of binding N-myristoylated 5-mer peptides and presenting them to specific CTLs. A high-resolution X-ray crystallographic analysis of the MHC class I:lipopeptide complex reveals an Ag-binding groove that is elaborately constructed to bind N-myristoylated short peptides rather than prototypic 9-mer peptides. The identification of lipopeptide-specific, MHC class I-restricted CTLs indicates that the widely accepted concept of MHC class I-mediated presentation of long peptides to CTLs may need some modifications to incorporate a novel MHC class I function of lipopeptide Ag presentation.","bibjson":{"author":[{"initials":"D","lastname":"Morita","name":"Morita D"},{"initials":"Y","lastname":"Yamamoto","name":"Yamamoto Y"},{"initials":"T","lastname":"Mizutani","name":"Mizutani T"},{"initials":"T","lastname":"Ishikawa","name":"Ishikawa T"},{"initials":"J","lastname":"Suzuki","name":"Suzuki J"},{"initials":"T","lastname":"Igarashi","name":"Igarashi T"},{"initials":"N","lastname":"Mori","name":"Mori N"},{"initials":"T","lastname":"Shiina","name":"Shiina T"},{"initials":"H","lastname":"Inoko","name":"Inoko H"},{"initials":"H","lastname":"Fujita","name":"Fujita H"},{"initials":"K","lastname":"Iwai","name":"Iwai K"},{"initials":"Y","lastname":"Tanaka","name":"Tanaka Y"},{"initials":"B","lastname":"Mikami","name":"Mikami B"},{"initials":"M","lastname":"Sugita","name":"Sugita M"}],"identifier":[{"id":"10.1038/ncomms10356","type":"doi"},{"id":"26758274","type":"pubmed"}],"issue":[null],"journal":{"iso_abbreviation":"Nat Commun","name":""},"pages":["10356"],"title":"Crystal structure of the N-myristoylated lipopeptide-bound MHC class I complex.","type":"article","url":"http://www.nature.com/articles/ncomms10356","volume":["7"],"year":[2016]},"in_pmc":"N","in_pmce":"Y","open_access":"Y"},"resolution":"1.76","same_as":{"pdbe":{"url":"https://www.ebi.ac.uk/pdbe/entry/pdb/4zfz"},"rcsb":{"url":"https://www.rcsb.org/structure/4zfz"}},"species":{"common_name":"rhesus monkey","match_type":"histo:assign_species","scientific_name":"Macaca mulatta","slug":"macaca_mulatta"},"tcr":null,"title":"Mamu-B*098:08 binding \"GGAIS\" at 1.76Å resolution","unique_chain_count":3}}