Determinants of the Peptide-induced Conformational Change in the Human Class II Major Histocompatibility Complex Protein

The human class II major histocompatibility complex protein HLA-DR1 has been shown previously to undergo a distinct conformational change from an open to a com-pact form upon binding peptide. To investigate the role of peptide in triggering the conformational change, the minimal requirements for inducing the compact confor-mation were determined. Peptides as short as two and four residues, which occupy only a small fraction of the peptide-binding cleft, were able to induce the conforma-tional change. A mutant HLA-DR1 protein with a substi-tution in the b subunit designed to fill the P1 pocket from within the protein (Gly86 to Tyr) adopted to a large extent the compact, peptide-bound conformation. Inter-actions important in stabilizing the compact conforma-tion are shown to be distinct from those responsible fo