5DDH

Structure of HLA-A2:01 with the 12-mer peptide F12K

Summary for 5DDH

• Entry DOI: 10.2210/pdb5ddh/pdb
• Related: 5D9S
• Descriptor: HLA class I histocompatibility antigen, A-2 alpha chain, Beta-2-microglobulin, 12-mer peptide F12K, ... (5 entities in total)
• Functional Keywords: mhc, immune system, peptide-protein complex
• Biological source: Homo sapiens (Human); More
• Cellular location: Membrane; Single-pass type I membrane protein: P01892; Secreted : P61769
• Total number of polymer chains: 3
• Total formula weight: 45056.06

Authors

Remesh, S.G.,Zajonc, D. (deposition date: 2015-08-24, release date: 2016-07-27, Last modification date: 2024-11-06)

Primary citation

McMurtrey, C.,Trolle, T.,Sansom, T.,Remesh, S.G.,Kaever, T.,Bardet, W.,Jackson, K.,McLeod, R.,Sette, A.,Nielsen, M.,Zajonc, D.M.,Blader, I.J.,Peters, B.,Hildebrand, W.
Toxoplasma gondii peptide ligands open the gate of the HLA class I binding groove.
Elife, 5:-, 2016

PubMed Abstract: HLA class I presentation of pathogen-derived peptide ligands is essential for CD8+ T-cell recognition of Toxoplasma gondii infected cells. Currently, little data exist pertaining to peptides that are presented after T. gondii infection. Herein we purify HLA-A*02:01 complexes from T. gondii infected cells and characterize the peptide ligands using LCMS. We identify 195 T. gondii encoded ligands originating from both secreted and cytoplasmic proteins. Surprisingly, T. gondii ligands are significantly longer than uninfected host ligands, and these longer pathogen-derived peptides maintain a canonical N-terminal binding core yet exhibit a C-terminal extension of 1-30 amino acids. Structural analysis demonstrates that binding of extended peptides opens the HLA class I F' pocket, allowing the C-terminal extension to protrude through one end of the binding groove. In summary, we demonstrate that unrealized structural flexibility makes MHC class I receptive to parasite-derived ligands that exhibit unique C-terminal peptide extensions.

PubMed: 26824387
DOI: 10.7554/eLife.12556

Experimental method

X-RAY DIFFRACTION (1.5 Å)