6TDS

Crystal structure of the disulfide engineered HLA-A0201 molecule without peptide bound after NaCl wash

Summary for 6TDS

• Entry DOI: 10.2210/pdb6tds/pdb
• Descriptor: MHC class I antigen, Beta-2-microglobulin, 1,2-ETHANEDIOL, ... (6 entities in total)
• Functional Keywords: mhc class i molecule, immune system
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 4
• Total formula weight: 88672.39

Authors

Anjanappa, R.,Garcia Alai, M.,Springer, S.,Meijers, R. (deposition date: 2019-11-10, release date: 2020-03-25, Last modification date: 2024-11-20)

Primary citation

Anjanappa, R.,Garcia-Alai, M.,Kopicki, J.D.,Lockhauserbaumer, J.,Aboelmagd, M.,Hinrichs, J.,Nemtanu, I.M.,Uetrecht, C.,Zacharias, M.,Springer, S.,Meijers, R.
Structures of peptide-free and partially loaded MHC class I molecules reveal mechanisms of peptide selection.
Nat Commun, 11:1314-1314, 2020

PubMed Abstract: Major Histocompatibility Complex (MHC) class I molecules selectively bind peptides for presentation to cytotoxic T cells. The peptide-free state of these molecules is not well understood. Here, we characterize a disulfide-stabilized version of the human class I molecule HLA-A*02:01 that is stable in the absence of peptide and can readily exchange cognate peptides. We present X-ray crystal structures of the peptide-free state of HLA-A*02:01, together with structures that have dipeptides bound in the A and F pockets. These structural snapshots reveal that the amino acid side chains lining the binding pockets switch in a coordinated fashion between a peptide-free unlocked state and a peptide-bound locked state. Molecular dynamics simulations suggest that the opening and closing of the F pocket affects peptide ligand conformations in adjacent binding pockets. We propose that peptide binding is co-determined by synergy between the binding pockets of the MHC molecule.

PubMed: 32161266
DOI: 10.1038/s41467-020-14862-4

Experimental method

X-RAY DIFFRACTION (1.7 Å)