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

Abstract

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.

Journal

• Nature Communications

  Nature Communications 7 2016-01-13

  Nature Publishing Group

Keywords

• Biological sciences
• Biochemistry
• Immunology

Details

• CRID: 1050845760760125952
• NII Article ID: 120005743661
• ISSN: 20411723
• HANDLE: 2433/210221
• Text Lang: en
• Article Type: journal article
• Data Source:
  • IRDB
  • CiNii Articles