Paper Citing NAMD - Abstract
Mage, Michael G.; Dolan, Michael A.; Wang, Rui; Boyd, Lisa F.; Revilleza, Maria Jamela; Robinson, Howard; Natarajan, Kannan; Myers, Nancy B.; Hansen, Ted H.; Margulies, David H.
The Peptide-Receptive Transition State of MHC Class I Molecules: Insight from Structure and Molecular Dynamics
JOURNAL OF IMMUNOLOGY, 189:1391-1399, AUG 1 2012
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 Journal of Immunology, 2012, 189: 1391-1399.
