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Cutting edge: HLA-DM-mediated peptide exchange functions normally on MHC class II-peptide complexes that have been weakened by elimination of a conserved hydrogen bond.

TitleCutting edge: HLA-DM-mediated peptide exchange functions normally on MHC class II-peptide complexes that have been weakened by elimination of a conserved hydrogen bond.
Publication TypeJournal Article
Year of Publication2010
AuthorsFerrante, A, Gorski, J
JournalJ Immunol
Volume184
Issue3
Pagination1153-8
Date Published2010 Feb 1
ISSN1550-6606
KeywordsAmino Acid Substitution, Binding, Competitive, Cell Line, Conserved Sequence, Hemagglutinin Glycoproteins, Influenza Virus, HLA-D Antigens, HLA-DR1 Antigen, Humans, Hydrogen Bonding, Influenza A virus, Ligands, Multiprotein Complexes, Mutagenesis, Site-Directed, Peptide Fragments, Protein Binding, Protein Conformation, Protein Folding, Protein Stability
Abstract

The mechanism by which HLA-DM (DM) promotes exchange of peptides bound to HLA-DR (DR) is still unclear. We have shown that peptide interaction with DR1 can be considered a folding process as evidenced by cooperativity. However, in DM-mediated ligand exchange, prebound peptide release is noncooperative, which could be a function of the breaking of a critical interaction. The hydrogen bond (H-bond) between beta-chain His(81) and the peptide backbone at the -1 position is a candidate for such a target. In this study, we analyze the exchange of peptides bound to a DR1 mutant in which formation of this H-bond is impaired. We observe that DM still functions normally. However, as expected of a cooperative model, this H-bond contributes to the overall energetics of the complex and its disruption impacts the ability of the exchange ligand to fold with the binding groove into a stable complex.

DOI10.4049/jimmunol.0902878
Alternate JournalJ. Immunol.
PubMed ID20038641
Grant ListR01AI63016 / AI / NIAID NIH HHS / United States
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