Crystal structure of the human class II MHC protein HLA-DR1 complexed with an influenza virus peptide

• Published in: Nature (London) Vol. 368; no. 6468; pp. 215 - 221
• Main Authors: Stern, Lawrence J, Brown, Jerry H, Jardetzky, Theodore S, Gorga, Joan C, Urban, Robert G, Strominger, Jack L, Wiley, Don C
• Format: Journal Article
• Language: English
• Published: London Nature Publishing 17-03-1994; Nature Publishing Group
• Subjects: Amino Acid Sequence; Antigens; Binding Sites; Biochemistry; Biological and medical sciences; Crystallography, X-Ray; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Hemagglutinin Glycoproteins, Influenza Virus; Hemagglutinins - chemistry; Hemagglutinins, Viral - chemistry; Histocompatibility antigens (hla, h-2 and other systems); HLA-DR1 Antigen - chemistry; HLA-DR1 Antigen - metabolism; Humans; Hydrogen Bonding; Influenza; Influenza virus; Models, Molecular; Molecular immunology; Molecular Sequence Data; Peptide Fragments - chemistry; Protein Binding; Protein Conformation; Proteins; Receptors, Antigen, T-Cell - metabolism; Virus; Human; Peptides; Gene product; Major histocompatibility system; Class II histocompatibility antigen; Orthomyxoviridae; Molecular complex; HLA-DR-Locus; Influenzavirus; Crystalline structure
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/368215a0

An influenza virus peptide binds to HLA-DR1 in an extended conformation with a pronounced twist. Thirty-five per cent of the peptide surface is accessible to solvent and potentially available for interaction with the antigen receptor on T cells. Pockets in the peptide-binding site accommodate five of the thirteen side chains of the bound peptide, and explain the peptide specificity of HLA-DR1. Twelve hydrogen bonds between conserved HLA-DR1 residues and the main chain of the peptide provide a universal mode of peptide binding, distinct from the strategy used by class I histocompatibility proteins.