7WT4

Crystal structure of HLA-A*2402 complexed with 8-mer Influenza PB1 peptide

Summary for 7WT4

• Entry DOI: 10.2210/pdb7wt4/pdb
• Descriptor: MHC class I antigen, Beta-2-microglobulin, PB1 peptide, ... (8 entities in total)
• Functional Keywords: mhc class i, antigen presentation, immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 6
• Total formula weight: 92639.73

Authors

Asa, M.,Morita, D.,Sugita, M. (deposition date: 2022-02-03, release date: 2022-06-22, Last modification date: 2024-10-16)

Primary citation

Asa, M.,Morita, D.,Kuroha, J.,Mizutani, T.,Mori, N.,Mikami, B.,Sugita, M.
Crystal structures of N-myristoylated lipopeptide-bound HLA class I complexes indicate reorganization of B-pocket architecture upon ligand binding.
J.Biol.Chem., 298:102100-102100, 2022

PubMed Abstract: Rhesus monkeys have evolved MHC-encoded class I allomorphs such as Mamu-B∗098 that are capable of binding N-myristoylated short lipopeptides rather than conventional long peptides; however, it remains unknown whether such antigen-binding molecules exist in other species, including humans. We herein demonstrate that human leukocyte antigen (HLA)-A∗24:02 and HLA-C∗14:02 proteins, which are known to bind conventional long peptides, also have the potential to bind N-myristoylated short lipopeptides. These HLA class I molecules shared a serine at position 9 (Ser9) with Mamu-B∗098, in contrast to most MHC class I molecules that harbor a larger amino acid residue, such as tyrosine, at this position. High resolution X-ray crystallographic analyses of lipopeptide-bound HLA-A∗24:02 and HLA-C∗14:02 complexes indicated that Ser9 was at the bottom of the B pocket with its small hydroxymethyl side chain directed away from the B-pocket cavity, thereby contributing to the formation of a deep hydrophobic cavity suitable for accommodating the long-chain fatty acid moiety of lipopeptide ligands. Upon peptide binding, however, we found the hydrogen-bond network involving Ser9 was reorganized, and the remodeled B pocket was able to capture the second amino acid residue (P2) of peptide ligands. Apart from the B pocket, virtually no marked alterations were observed for the A and F pockets upon peptide and lipopeptide binding. Thus, we concluded that the structural flexibility of the large B pocket of HLA-A∗2402 and HLA-C∗1402 primarily accounted for their previously unrecognized capacity to bind such chemically distinct ligands as conventional peptides and N-myristoylated lipopeptides.

PubMed: 35667438
DOI: 10.1016/j.jbc.2022.102100

Experimental method

X-RAY DIFFRACTION (1.89459140677 Å)