Document Detail

Conformational variation in structures of classical and non-classical MHCII proteins and functional implications.
MedLine Citation:
PMID:  23046127     Owner:  NLM     Status:  MEDLINE    
Recent structural characterizations of classical and non-classical major histocompatibility complex class II (MHCII) proteins have provided a view into the dynamic nature of the MHCII-peptide binding groove and the role that structural changes play in peptide loading processes. Although there have been numerous reports of crystal structures for MHCII-peptide complexes, a detailed analysis comparing all the structures has not been reported, and subtle conformational variations present in these structures may not have been fully appreciated. We compared the 91 MHCII crystal structures reported in the PDB to date, including an HLA-DR mutant particularly susceptible to DM-mediated peptide exchange, and reviewed experimental and computational studies of the effect of peptide binding on MHCII structure. These studies provide evidence for conformational lability in and around the α-subunit 3-10 helix at residues α48-51, a region known to be critical for HLA-DM-mediated peptide exchange. A biophysical study of MHC-peptide hydrogen bond strengths and a recent structure of the non-classical MHCII protein HLA-DO reveal changes in the same region. Conformational variability was observed also in the vicinity of a kink in the β-subunit helical region near residue β66 and in the orientation and loop conformation in the β2 Ig domain. Here, we provide an overview of the regions within classical and non-classical MHCII proteins that display conformational changes and the potential role that these changes may have in the peptide loading/exchange process.
Corrie A Painter; Lawrence J Stern
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Review    
Journal Detail:
Title:  Immunological reviews     Volume:  250     ISSN:  1600-065X     ISO Abbreviation:  Immunol. Rev.     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-10-10     Completed Date:  2013-02-25     Revised Date:  2013-11-06    
Medline Journal Info:
Nlm Unique ID:  7702118     Medline TA:  Immunol Rev     Country:  England    
Other Details:
Languages:  eng     Pagination:  144-57     Citation Subset:  IM    
Copyright Information:
© 2012 John Wiley & Sons A/S.
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, USA.
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MeSH Terms
Antigen Presentation*
Binding Sites
Crystallography, X-Ray
HLA-D Antigens / chemistry*,  immunology,  metabolism
HLA-DR Antigens / chemistry*,  immunology,  metabolism
Histocompatibility Antigens Class II / chemistry*,  immunology,  metabolism
Hydrogen Bonding
Models, Molecular
Peptides / chemistry*,  immunology,  metabolism
Protein Binding
Protein Structure, Secondary
Protein Structure, Tertiary
Grant Support
Reg. No./Substance:
0/HLA-D Antigens; 0/HLA-DO antigens; 0/HLA-DR Antigens; 0/Histocompatibility Antigens Class II; 0/Peptides

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