title: Bound water structure and polymorphic amino acids act together to allow the binding of different peptides to MHC class I HLA-B53.
abstract: The structure of the human MHC class I molecule HLA-B53 complexed to two nonameric peptide epitopes (from the malaria parasite P. falciparum and the HIV2 gag protein) has been determined by X-ray crystallography at 2.3 angstrom resolution. The structures reveal the architecture of a Pro-specific B pocket common to many HLA-B alleles. Relative to other alleles, the B53 peptide-binding groove is widened by a significant (up to 1.25 angstrom) shift in the position of the alpha 1 helix. Within this groove, bound water molecules, acting in concert with the side chains of polymorphic residues, provide the functional malleability of the MHC, which enables the high affinity/low specificity binding of multiple peptide epitopes.
authors.affiliation: Nuffield Department of Clinical Medicine, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, United Kingdom.
authors.forename: K J
authors.initials: KJ
authors.lastname: Smith
authors.forename: S W
authors.initials: SW
authors.lastname: Reid
authors.forename: K
authors.initials: K
authors.lastname: Harlos
authors.forename: A J
authors.initials: AJ
authors.lastname: McMichael
authors.forename: D I
authors.initials: DI
authors.lastname: Stuart
authors.forename: J I
authors.initials: JI
authors.lastname: Bell
authors.forename: E Y
authors.initials: EY
authors.lastname: Jones
mesh_terms: D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry*; D001483:Base Sequence; D018360:Crystallography, X-Ray; D006680:HLA Antigens / Q000737:chemistry*; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry*; D011110:Polymorphism, Genetic / Q000276:immunology*; D011485:Protein Binding / Q000276:immunology; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D014867:Water / Q000737:chemistry*
chemical_list: D000596:Amino Acids; D006680:HLA Antigens; C078438:HLA-B53 antigen; D010455:Peptides; D014867:Water