Document Detail


A structural and molecular dynamics approach to understanding the peptide-receptive transition state of MHC-I molecules.
MedLine Citation:
PMID:  23200143     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Michael G Mage; Michael A Dolan; Rui Wang; Lisa F Boyd; Maria Jamela Revilleza; Howard Robinson; Kannan Natarajan; Nancy B Myers; Ted H Hansen; David H Margulies
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, N.I.H., Intramural; Review     Date:  2012-11-28
Journal Detail:
Title:  Molecular immunology     Volume:  55     ISSN:  1872-9142     ISO Abbreviation:  Mol. Immunol.     Publication Date:  2013 Sep 
Date Detail:
Created Date:  2013-03-29     Completed Date:  2013-06-17     Revised Date:  2014-09-02    
Medline Journal Info:
Nlm Unique ID:  7905289     Medline TA:  Mol Immunol     Country:  England    
Other Details:
Languages:  eng     Pagination:  123-5     Citation Subset:  IM    
Copyright Information:
Published by Elsevier Ltd.
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MeSH Terms
Descriptor/Qualifier:
Antibodies, Monoclonal / immunology,  metabolism
Antigen Presentation
CD8-Positive T-Lymphocytes / immunology*
Crystallography, X-Ray
Histocompatibility Antigens Class I / immunology*,  metabolism
Humans
Molecular Dynamics Simulation*
Protein Binding
Protein Structure, Tertiary
Receptors, Pattern Recognition / immunology*,  ultrastructure*
Grant Support
ID/Acronym/Agency:
AI019687/AI/NIAID NIH HHS; P30 EB009998/EB/NIBIB NIH HHS; R01 AI019687/AI/NIAID NIH HHS; ZIA AI000394-29/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Histocompatibility Antigens Class I; 0/Receptors, Pattern Recognition
Comments/Corrections

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