The structure of HLA-DM, the peptide exchange catalyst that loads antigen onto class II MHC molecules during antigen presentation

Immunity. 1998 Sep;9(3):377-83. doi: 10.1016/s1074-7613(00)80620-2.

Abstract

The three-dimensional structure of the soluble ecto-domain of HLA-DM has been determined to 2.5 A resolution by X-ray crystallography. HLA-DM has both peptide exchange activity and acts as a chaperone to peptide-free class II MHC molecules. As predicted, the structure is similar to that of classical class II MHC molecules except that the peptide-binding site is altered to an almost fully closed groove. An unusual cavity is found at the center of the region that binds peptides in class II MHC molecules, and a tryptophanrich lateral surface is identified that is a candidate both for binding to HLA-DR, to effect catalysis, and to HLA-DO, an inhibitor.

Publication types

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

MeSH terms

  • Antigen Presentation / physiology
  • Antigens / metabolism
  • Catalysis
  • Crystallography, X-Ray
  • HLA-D Antigens / chemistry*
  • HLA-DR Antigens / chemistry
  • Histocompatibility Antigens Class II / metabolism
  • Humans
  • Molecular Sequence Data
  • Peptides / immunology
  • Protein Conformation
  • Sequence Homology, Amino Acid
  • Species Specificity

Substances

  • Antigens
  • H2-M antigens
  • HLA-D Antigens
  • HLA-DM antigens
  • HLA-DR Antigens
  • Histocompatibility Antigens Class II
  • Peptides

Associated data

  • PDB/1HDM