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

Biochemistry. 1999 May 4;38(18):5878-87. doi: 10.1021/bi983048m.

Abstract

To investigate a conformational change accompanying peptide binding to class II MHC proteins, we probed the structure of a soluble version of the human class II MHC protein HLA-DR1 in empty and peptide-loaded forms. Peptide binding induced a large decrease in the effective radius of the protein as determined by gel filtration, dynamic light scattering, and analytical ultracentrifugation. It caused a substantial increase in the cooperativity of thermal denaturation and induced alterations in MHC polypeptide backbone structure as determined by circular dichroism. These changes suggest a condensation of the protein around the bound peptide. An antibody specific for beta58-69 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 of intracellular antigen presentation pathways.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Antibodies, Monoclonal / metabolism
  • Circular Dichroism
  • HLA-DR1 Antigen / chemistry*
  • HLA-DR1 Antigen / genetics
  • HLA-DR1 Antigen / immunology
  • HLA-DR1 Antigen / metabolism*
  • Humans
  • Hydrogen-Ion Concentration
  • Kinetics
  • Models, Molecular
  • Molecular Sequence Data
  • Peptides / chemistry
  • Peptides / genetics
  • Peptides / metabolism*
  • Protein Binding / genetics
  • Protein Conformation
  • Protein Folding
  • Protein Structure, Secondary
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism
  • Thermodynamics

Substances

  • Antibodies, Monoclonal
  • HLA-DR1 Antigen
  • Peptides
  • Recombinant Proteins