6LB2

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

Summary for 6LB2

• Entry DOI: 10.2210/pdb6lb2/pdb
• Related: 6LAH 6LAM
• Descriptor: MHC class I antigen, Beta-2-microglobulin, ZINC ION, ... (6 entities in total)
• Functional Keywords: mhc class i protein, complex, mono-acyl glycerol, immune system
• Biological source: Macaca mulatta (Rhesus macaque); More
• Total number of polymer chains: 4
• Total formula weight: 90501.42

Authors

Shima, Y.,Morita, D. (deposition date: 2019-11-13, release date: 2020-04-22, Last modification date: 2024-10-30)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.69380954073 Å)