Journal Article Crystal structure of the N-myristoylated lipopeptide-bound MHC class i complex

Morita, Daisuke  ,  Yamamoto, Yukie  ,  Mizutani, Tatsuaki  ,  Ishikawa, Takeshi  ,  Suzuki, Juri  ,  Igarashi, Tatsuhiko  ,  Mori, Naoki  ,  Shiina, Takashi  ,  Inoko, Hidetoshi  ,  Fujita, Hiroaki  ,  Iwai, Kazuhiro  ,  Tanaka, Yoshimasa  ,  Mikami, Bunzo  ,  Sugita, Masahiko

72016-01-13 , Nature Publishing Group
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.

Number of accesses :  

Other information