8E8I

Structures of HLA-B8E76C loaded with long peptides reveal novel features at the N-terminus of the groove

Summary for 8E8I

• Entry DOI: 10.2210/pdb8e8i/pdb
• Descriptor: MHC class I antigen, Beta-2-microglobulin, PHE-VAL-LYS-LYS-LYS-TYR-CYS-LEU, ... (4 entities in total)
• Functional Keywords: mhc class i, antigen processing and presentation, long peptides, hla-b8, immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 3
• Total formula weight: 44812.69

Authors

Li, L.,Bouvier, M. (deposition date: 2022-08-25, release date: 2023-07-26, Last modification date: 2024-11-20)

Primary citation

Li, L.,Peng, X.,Batliwala, M.,Bouvier, M.
Crystal structures of MHC class I complexes reveal the elusive intermediate conformations explored during peptide editing.
Nat Commun, 14:5020-5020, 2023

PubMed Abstract: Studies have suggested that MHC class I (MHC I) molecules fluctuate rapidly between numerous conformational states and these motions support peptide sampling. To date, MHC I intermediates are largely uncharacterized experimentally and remain elusive. Here, we present x-ray crystal structures of HLA-B8 loaded with 20mer peptides that show pronounced distortions at the N-terminus of the groove. Long stretches of N-terminal amino acid residues are missing in the electron density maps creating an open-ended groove. Our structures also reveal highly unusual features in MHC I-peptide interaction at the N-terminus of the groove. Molecular dynamics simulations indicate that the complexes have varying degrees of conformational flexibility in a manner consistent with the structures. We suggest that our structures have captured the remarkable molecular dynamics of MHC I-peptide interaction. The visualization of peptide-dependent conformational motions in MHC I is a major step forward in our conceptual understanding of dynamics in high-affinity peptide selection.

PubMed: 37596268
DOI: 10.1038/s41467-023-40736-6

Experimental method

X-RAY DIFFRACTION (1.49 Å)