A conformational change in the human major histocompatibility complex protein HLA-DR1 induced by peptide binding

To investigate a conformational change accompanying peptide binding to clas s II MHC proteins, we probed the structure of a soluble version of the huma n class II MHC protein HLA-DR1 in empty and peptide-loaded forms. Peptide b inding induced a large decrease in the effective radius of the protein as d etermined by gel filtration, dynamic light scattering, and analytical ultra centrifugation. It caused a substantial increase in the cooperativity of th ermal denaturation and induced alterations in MHC polypeptide backbone stru cture as determined by circular dichroism. These changes suggest a condensa tion of the protein around the bound peptide. An antibody specific for beta 58-69 preferentially bound the empty protein, indicating that the peptide- induced conformational change involves the beta-subunit helical region. The conformational change may have important implications for the mechanisms o f intracellular antigen presentation pathways.