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Publication Abstract from PubMed

The 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.

Crystal structure of the N-myristoylated lipopeptide-bound MHC class I complex.,Morita D, Yamamoto Y, Mizutani T, Ishikawa T, Suzuki J, Igarashi T, Mori N, Shiina T, Inoko H, Fujita H, Iwai K, Tanaka Y, Mikami B, Sugita M Nat Commun. 2016 Jan 13;7:10356. doi: 10.1038/ncomms10356. PMID:26758274^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.