Bound water structure and polymorphic amino acids act together to allow the binding of different peptides to MHC class I HLA-B53.
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.
Smith
K J
KJ
Nuffield Department of Clinical Medicine, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, United Kingdom.
Reid
S W
SW
Harlos
K
K
McMichael
A J
AJ
Stuart
D I
DI
Bell
J I
JI
Jones
E Y
EY
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*
D000596:Amino Acids; D006680:HLA Antigens; C078438:HLA-B53 antigen; D010455:Peptides; D014867:Water