The three-dimensional structure of a class I major histocompatibility complex molecule missing the alpha 3 domain of the heavy chain.
Class I major histocompatibility complex (MHC) molecules are ternary complexes of the soluble serum protein beta 2-microglobulin, MHC heavy chain, and bound peptide. The first two domains (alpha 1, alpha 2) of the heavy chain create the peptide binding cleft and the surface that contacts the T-cell receptor. The third domain (alpha 3) associates with the T-cell co-receptor, CD8, during T-cell recognition. Here we describe the x-ray crystal structure of a human class I MHC molecule, HLA-Aw68, from which the alpha 3 domain has been proteolytically removed. The resulting molecule shows no gross morphological changes compared to the intact protein. A decameric peptide complexed with the intact HLA-Aw68 is seen to bind to the proteolized molecule in the conventional manner, demonstrating that the alpha 3 domain is not required for the structural integrity of the molecule or for peptide binding.
Collins
E J
EJ
Department of Molecular and Cellular Biology, Howard Hughes Medical Institute, Harvard University, Cambridge, MA 02138.
Garboczi
D N
DN
Karpusas
M N
MN
Wiley
D C
DC
D000595:Amino Acid Sequence; D002460:Cell Line; D018360:Crystallography, X-Ray; D015234:HLA-A Antigens / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D006868:Hydrolysis; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary
D015234:HLA-A Antigens; C053029:HLA-A*68 antigen; D010446:Peptide Fragments