title: Crystal structure of the N-myristoylated lipopeptide-bound MHC class I complex.
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.
authors.affiliation: Laboratory of Cell Regulation, Institute for Virus Research, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.|Laboratory of Cell Regulation and Molecular Network, Graduate School of Biostudies, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Morita
authors.affiliation: Laboratory of Cell Regulation, Institute for Virus Research, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.|Laboratory of Cell Regulation and Molecular Network, Graduate School of Biostudies, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Yukie
authors.initials: Y
authors.lastname: Yamamoto
authors.affiliation: Laboratory of Cell Regulation, Institute for Virus Research, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Tatsuaki
authors.initials: T
authors.lastname: Mizutani
authors.affiliation: Department of Molecular Microbiology and Immunology, Graduate School of Biomedical Sciences, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Ishikawa
authors.affiliation: Center for Human Evolution Modeling Research, Primate Research Institute, Kyoto University, Inuyama, Aichi 484-8506, Japan.
authors.forename: Juri
authors.initials: J
authors.lastname: Suzuki
authors.affiliation: Center for Emerging Virus Research, Institute for Virus Research, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Igarashi
authors.affiliation: Laboratory of Chemical Ecology, Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Kitashirakawa-Oiwake-cho, Sakyo-ku, Kyoto 606-8502, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Mori
authors.affiliation: Division of Basic Medical Science and Molecular Medicine, Department of Molecular Life Science, Tokai University School of Medicine, Isehara, Kanagawa 259-1143, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Shiina
authors.affiliation: Division of Basic Medical Science and Molecular Medicine, Department of Molecular Life Science, Tokai University School of Medicine, Isehara, Kanagawa 259-1143, Japan.
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Inoko
authors.affiliation: Department of Molecular and Cellular Physiology, Graduate School of Medicine, Kyoto University, Yoshida-konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Fujita
authors.affiliation: Department of Molecular and Cellular Physiology, Graduate School of Medicine, Kyoto University, Yoshida-konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Iwai
authors.affiliation: Center for Bioinformatics and Molecular Medicine, Graduate School of Biomedical Sciences, Nagasaki University, 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan.
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Tanaka
authors.affiliation: Laboratory of Applied Structural Biology, Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Gokasho, Uji, Kyoto 611-0011, Japan.
authors.forename: Bunzo
authors.initials: B
authors.lastname: Mikami
authors.affiliation: Laboratory of Cell Regulation, Institute for Virus Research, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.|Laboratory of Cell Regulation and Molecular Network, Graduate School of Biostudies, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Sugita
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D003460:Crystallization; D015395:Histocompatibility Antigens Class I / Q000737:chemistry / Q000378:metabolism*; D008074:Lipoproteins / Q000378:metabolism; D008253:Macaca mulatta; D008969:Molecular Sequence Data; D015394:Molecular Structure; D019814:Myristic Acid / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*
chemical_list: D015395:Histocompatibility Antigens Class I; D008074:Lipoproteins; D011948:Receptors, Antigen, T-Cell; D019814:Myristic Acid