3v52

Publication Abstract from PubMed

MHC class I (MHC-I) proteins of the adaptive immune system require antigenic peptides for maintenance of mature conformation and immune function via specific recognition by MHC-I-restricted CD8(+) T lymphocytes. New MHC-I molecules in the endoplasmic reticulum are held by chaperones in a peptide-receptive (PR) transition state pending release by tightly binding peptides. In this study, we show, by crystallographic, docking, and molecular dynamics methods, dramatic movement of a hinged unit containing a conserved 3(10) helix that flips from an exposed "open" position in the PR transition state to a "closed" position with buried hydrophobic side chains in the peptide-loaded mature molecule. Crystallography of hinged unit residues 46-53 of murine H-2L(d) MHC-I H chain, complexed with mAb 64-3-7, demonstrates solvent exposure of these residues in the PR conformation. Docking and molecular dynamics predict how this segment moves to help form the A and B pockets crucial for the tight peptide binding needed for stability of the mature peptide-loaded conformation, chaperone dissociation, and Ag presentation.

The Peptide-receptive transition state of MHC class I molecules: insight from structure and molecular dynamics.,Mage MG, Dolan MA, Wang R, Boyd LF, Revilleza MJ, Robinson H, Natarajan K, Myers NB, Hansen TH, Margulies DH J Immunol. 2012 Aug 1;189(3):1391-9. Epub 2012 Jun 29. PMID:22753930^[1]

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