6LAH

Crystal structure of rhesus macaque MHC class I molecule Mamu-B*098 complexed with lysophosphatidylcholine

6LAH の概要

• エントリーDOI: 10.2210/pdb6lah/pdb
• 分子名称: MHC class I antigen, Beta-2-microglobulin, ZINC ION, ... (6 entities in total)
• 機能のキーワード: mhc class i protein, complex, lysophospholipid, immune system
• 由来する生物種: Macaca mulatta (Rhesus macaque); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 89815.34

構造登録者

Shima, Y.,Morita, D. (登録日: 2019-11-12, 公開日: 2020-04-22, 最終更新日: 2024-11-06)

主引用文献

Shima, Y.,Morita, D.,Mizutani, T.,Mori, N.,Mikami, B.,Sugita, M.
Crystal structures of lysophospholipid-bound MHC class I molecules.
J.Biol.Chem., 295:6983-6991, 2020

PubMed Abstract: Newly synthesized major histocompatibility complex (MHC) class I proteins are stabilized in the endoplasmic reticulum (ER) by binding 8-10-mer-long self-peptide antigens that are provided by transporter associated with antigen processing (TAP). These MHC class I:peptide complexes then exit the ER and reach the plasma membrane, serving to sustain the steady-state MHC class I expression on the cell surface. A novel subset of MHC class I molecules that preferentially bind lipid-containing ligands rather than conventional peptides was recently identified. The primate classical MHC class I allomorphs, Mamu-B*098 and Mamu-B*05104, are capable of binding the -myristoylated 5-mer (C14-Gly-Gly-Ala-Ile-Ser) or 4-mer (C14-Gly-Gly-Ala-Ile) lipopeptides derived from the -myristoylated SIV Nef protein, respectively, and of activating lipopeptide antigen-specific cytotoxic T lymphocytes. We herein demonstrate that Mamu-B*098 samples lysophosphatidylethanolamine and lysophosphatidylcholine containing up to a C20 fatty acid in the ER. The X-ray crystal structures of Mamu-B*098 and Mamu-B*05104 complexed with lysophospholipids at high resolution revealed that the B and D pockets in the antigen-binding grooves of these MHC class I molecules accommodate these lipids through a monoacylglycerol moiety. Consistent with the capacity to bind cellular lipid ligands, these two MHC class I molecules did not require TAP function for cell-surface expression. Collectively, these results indicate that peptide- and lipopeptide-presenting MHC class I subsets use distinct sources of endogenous ligands.

PubMed: 32269076
DOI: 10.1074/jbc.RA119.011932

実験手法

X-RAY DIFFRACTION (1.87 Å)