5F7D

Structure of HLA-A2:01 with peptide G11N

Summary for 5F7D

• Entry DOI: 10.2210/pdb5f7d/pdb
• Descriptor: HLA class I histocompatibility antigen, A-2 alpha chain, Beta-2-microglobulin, Peptide G11N, ... (5 entities in total)
• Functional Keywords: peptide complex, mhc, immune system
• Biological source: Homo sapiens (Human); More
• Cellular location: Membrane; Single-pass type I membrane protein: P01892; Secreted . Note=(Microbial infection) In the presence of M: P61769
• Total number of polymer chains: 3
• Total formula weight: 44613.55

Authors

Zajonc, D.M.,Remesh, S.G. (deposition date: 2015-12-07, release date: 2016-12-21, Last modification date: 2024-10-16)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.3 Å)