REGULATION OF CONFORMATION AND LIGAND-BINDING FUNCTION OF INTEGRIN ALPHA-5-BETA-1 BY THE BETA-1 CYTOPLASMIC DOMAIN

We have studied the role of the cytoplasmic domain in the conformation and affinity modulation of the integrin beta 1. Expression of a confo rmation dependent anti-beta 1 antibody 15/7 correlates with activation in wild-type beta 1. Truncation of 16 carboxyl-terminal residues in t he cytoplasmic domain (the 762t beta 1 mutant) induces constitutive ex pression of the 15/7 epitope at a high level (which probably reflects a major conformational change of the extracellular domain) but does no t activate ligand binding. The dissociation of epitope expression and affinity suggests that the epitope expression reflects the conformatio n of nonligand binding sites of the extracellular domain of beta 1 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 nonliga nd binding region of beta 1 (within residues 354-425). The 762t mutant has apparently normal alpha/beta association, suggesting that the ove rexpression of the 15/7 epitope is not due to alpha/beta dissociation. The data suggest that the carboxyl-terminal 16 residues of the beta 1 cytoplasmic domain are critical for properly modulating conformation and affinity of beta 1 integrins.