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.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Amino Acid Substitution / genetics
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Amino Acid Substitution / immunology
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Binding, Competitive / genetics
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Binding, Competitive / immunology
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Cell Line
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Conserved Sequence* / genetics
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HLA-D Antigens / metabolism
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HLA-D Antigens / physiology*
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HLA-DR1 Antigen / genetics
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HLA-DR1 Antigen / metabolism
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Hemagglutinin Glycoproteins, Influenza Virus / genetics
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Hemagglutinin Glycoproteins, Influenza Virus / metabolism
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Hemagglutinin Glycoproteins, Influenza Virus / physiology
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Humans
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Hydrogen Bonding
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Influenza A virus / immunology
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Ligands
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Multiprotein Complexes / genetics
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Multiprotein Complexes / metabolism
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Multiprotein Complexes / physiology*
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Mutagenesis, Site-Directed
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Peptide Fragments / genetics
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Peptide Fragments / metabolism*
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Peptide Fragments / physiology
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Protein Binding / genetics
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Protein Binding / immunology
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Protein Conformation
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Protein Folding
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Protein Stability
Substances
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HLA-D Antigens
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HLA-DM antigens
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HLA-DR1 Antigen
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Hemagglutinin Glycoproteins, Influenza Virus
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Ligands
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Multiprotein Complexes
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Peptide Fragments