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Mol Immunol. 2013 Sep;55(2):123-5. doi: 10.1016/j.molimm.2012.10.021. Epub 2012 Nov 28.

A structural and molecular dynamics approach to understanding the peptide-receptive transition state of MHC-I molecules.

Author information

  • 1Molecular Biology Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases NIAID, NIH, Bethesda, MD 20892-1892, USA. mmage@mail.nih.gov

Abstract

The mature conformation of major histocompatibility complex class I (MHC-I) proteins depends on the presence of bound peptides, permitting recognition at the cell surface by CD8(+) T lymphocytes. Newly synthesized MHC-I molecules in the endoplasmic reticulum are maintained in a peptide-receptive (PR) transition state by several chaperones until they are released concomitant with the loading of peptides. By determining the crystallographic structure of a region of an MHC-I molecule that is recognized by a unique monoclonal antibody and comparing this with docking and molecular dynamics simulations with the whole molecule, we demonstrate the movement of a hinged unit supporting the part of the binding groove that interacts with the amino terminal residues of the bound peptide. This unit contains a conserved 310 helix that flips from an exposed "open" position in the PR form to a "closed" position in the peptide-loaded (PL) mature molecule. These analyses indicate how this segment of the MHC-I molecule moves to help establish the A and B pockets critical for tight peptide binding and the stable structure required for antigen presentation and T cell recognition at the cell surface.

Published by Elsevier Ltd.

PMID:
23200143
[PubMed - indexed for MEDLINE]
PMCID:
PMC3632263
Free PMC Article
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