The structure of HLA-DM, the peptide exchange catalyst that loads antigen onto class II MHC molecules during antigen presentation.
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.
Department of Cellular and Molecular Biology, Howard Hughes Medical Institute, Harvard University, Cambridge, Massachusetts 02138, USA. mosyak@crystal.harvard.edu
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D017951:Antigen Presentation / Q000502:physiology; D000941:Antigens / Q000378:metabolism; D002384:Catalysis; D018360:Crystallography, X-Ray; D006681:HLA-D Antigens / Q000737:chemistry*; D006684:HLA-DR Antigens / Q000737:chemistry; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D010455:Peptides / Q000276:immunology; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity
D000941:Antigens; C416189:H2-M antigens; D006681:HLA-D Antigens; C084245:HLA-DM antigens; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II; D010455:Peptides