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Publication Abstract from PubMed

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.

Crystal structures of MHC class I complexes reveal the elusive intermediate conformations explored during peptide editing.,Li L, Peng X, Batliwala M, Bouvier M Nat Commun. 2023 Aug 18;14(1):5020. doi: 10.1038/s41467-023-40736-6. PMID:37596268^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.