title: Regulation of conformation and ligand binding function of integrin alpha5beta1 by the beta1 cytoplasmic domain.
abstract: We have studied the role of the cytoplasmic domain in the conformation and affinity modulation of the integrin beta1. Expression of a conformation-dependent anti-beta1 antibody 15/7 correlates with activation in wild-type beta1. Truncation of 16 carboxyl-terminal residues in the cytoplasmic domain (the 762t beta1 mutant) induces constitutive expression of the 15/7 epitope at a high level (which probably reflects a major conformational change of the extracellular domain) but does not activate ligand binding. The dissociation of epitope expression and affinity suggests that the epitope expression reflects the conformation of nonligand binding sites of the extracellular domain of beta1 but does not necessarily reflect that of the ligand binding sites. Indeed we discovered that the 15/7 epitope is in fact located in the nonligand binding region of beta1 (within residues 354-425). The 762t mutant has apparently normal alpha/beta association, suggesting that the overexpression of the 15/7 epitope is not due to alpha/beta dissociation. The data suggest that the carboxyl-terminal 16 residues of the beta1 cytoplasmic domain are critical for properly modulating conformation and affinity of beta1 integrins.
authors.affiliation: Department of Vascular Biology, The Scripps Research Institute, La Jolla, California 92037, USA.
authors.forename: W
authors.initials: W
authors.lastname: Puzon-McLaughlin
authors.forename: T A
authors.initials: TA
authors.lastname: Yednock
authors.forename: Y
authors.initials: Y
authors.lastname: Takada
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003593:Cytoplasm / Q000378:metabolism*; D018076:DNA, Complementary; D000939:Epitopes / Q000235:genetics; D006801:Humans; D008024:Ligands; D051379:Mice; D008969:Molecular Sequence Data; D016296:Mutagenesis; D011485:Protein Binding; D011487:Protein Conformation; D017469:Receptors, Fibronectin / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
chemical_list: D018076:DNA, Complementary; D000939:Epitopes; D008024:Ligands; D017469:Receptors, Fibronectin