Crystal structure of I-Ak in complex with a dominant epitope of lysozyme.
We have determined the structure of murine MHC class II I-Ak in complex with a naturally processed peptide from hen egg lysozyme (HEL residues 50-62) at 1.9 A resolution. These results provide a structural basis for the I-Ak peptide-binding motif. Binding is established by the deep burial of five anchor side chains into specific pockets of the I-Ak binding groove, with a zen-like fit of an aspartic acid in the P1 pocket. We also show that in the I-Ak alpha chain, a bulge occurs in the first strand of the peptide-binding platform, an insertion probably common to all I-A and HLA-DQ alleles. The I-Ak beta chain has a deletion in the helical region adjacent to the P7 pocket and an insertion in the helical region neighboring the P1 pocket. As a result of these structural features, the extended HEL peptide dips low into the center of the I-Ak groove and reaches toward solvent at its C-terminal end.
Fremont
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DH
Howard Hughes Medical Institute, Department of Biochemistry and Molecular Biophysics, Columbia University, New York, New York 10032, USA. fremont@immunology.wustl.edu
Monnaie
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D
Nelson
C A
CA
Hendrickson
W A
WA
Unanue
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ER
D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation; D001665:Binding Sites; D018360:Crystallography, X-Ray; D015798:HLA-DR1 Antigen; D000949:Histocompatibility Antigens Class II / Q000737:chemistry* / Q000235:genetics; D006860:Hydrogen Bonding; D016056:Immunodominant Epitopes / Q000737:chemistry*; D051379:Mice; D018448:Models, Immunological; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009113:Muramidase / Q000737:chemistry*; D010446:Peptide Fragments / Q000737:chemistry*; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000737:chemistry; D017386:Sequence Homology, Amino Acid
D015798:HLA-DR1 Antigen; D000949:Histocompatibility Antigens Class II; C111388:I-Ak antigen; D016056:Immunodominant Epitopes; D010446:Peptide Fragments; D011994:Recombinant Proteins; C111387:hen egg lysozyme peptide (50-62); D009113:Muramidase