4zfz
From Proteopedia
Crystal structure of rhesus macaque MHC class I molecule Mamu-B*098 complexed with myristoylated 5-mer lipopeptide derived from SIV Nef protein
Structural highlights
Function[NEF_SIVS4] Seems to play a role in optimizing the host cell environment for viral replication without causing cell death by apoptosis. Enhances virus infectivity and pathogenicity. Probably involved in viral immune evasion mechanisms (By similarity). In infected CD4(+) T-lymphocytes, down-regulates cell surface expression of CD4, CD28, CD3, and MHC-I or MHC-II molecules.[1] Interferes with TCR signaling from the cell membrane. Interacts with CD247/TCRZ (TCR zeta chain) and exert potent down-regulation of cell surface TCR/CD3 complexes.[2] [B2MG_MACMU] Component of the class I major histocompatibility complex (MHC). Involved in the presentation of peptide antigens to the immune system (By similarity). Publication Abstract from PubMedThe 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[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Categories: Morita, D | Sugita, M | Aid | Antigen presentation | Immune system | Lipopeptide | Mhc