5F9J

Structure of HLA-A2:01 with peptide Y9L

5F9J の概要

• エントリーDOI: 10.2210/pdb5f9j/pdb
• 分子名称: HLA class I histocompatibility antigen, A-2 alpha chain, Beta-2-microglobulin, Peptide Y9L, ... (5 entities in total)
• 機能のキーワード: peptide complex, mhc, immune system
• 由来する生物種: Homo sapiens (Human); 詳細
• 細胞内の位置: Membrane; Single-pass type I membrane protein: P01892; Secreted . Note=(Microbial infection) In the presence of M: P61769
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 44578.46

構造登録者

Remesh, S.G.,Zajonc, D.M. (登録日: 2015-12-09, 公開日: 2016-12-21, 最終更新日: 2024-10-16)

主引用文献

Remesh, S.G.,Andreatta, M.,Ying, G.,Kaever, T.,Nielsen, M.,McMurtrey, C.,Hildebrand, W.,Peters, B.,Zajonc, D.M.
Unconventional Peptide Presentation by Major Histocompatibility Complex (MHC) Class I Allele HLA-A*02:01: BREAKING CONFINEMENT.
J. Biol. Chem., 292:5262-5270, 2017

PubMed Abstract: Peptide antigen presentation by major histocompatibility complex (MHC) class I proteins initiates CD8 T cell-mediated immunity against pathogens and cancers. MHC I molecules typically bind peptides with 9 amino acids in length with both ends tucked inside the major A and F binding pockets. It has been known for a while that longer peptides can also bind by either bulging out of the groove in the middle of the peptide or by binding in a zigzag fashion inside the groove. In a recent study, we identified an alternative binding conformation of naturally occurring peptides from bound by HLA-A*02:01. These peptides were extended at the C terminus (PΩ) and contained charged amino acids not more than 3 residues after the anchor amino acid at PΩ, which enabled them to open the F pocket and expose their C-terminal extension into the solvent. Here, we show that the mechanism of F pocket opening is dictated by the charge of the first charged amino acid found within the extension. Although positively charged amino acids result in the Tyr-84 swing, amino acids that are negatively charged induce a not previously described Lys-146 lift. Furthermore, we demonstrate that the peptides with alternative binding modes have properties that fit very poorly to the conventional MHC class I pathway and suggest they are presented via alternative means, potentially including cross-presentation via the MHC class II pathway.

PubMed: 28179428
DOI: 10.1074/jbc.M117.776542

実験手法

X-RAY DIFFRACTION (2.51 Å)