W. Puzonmclaughlin et al., REGULATION OF CONFORMATION AND LIGAND-BINDING FUNCTION OF INTEGRIN ALPHA-5-BETA-1 BY THE BETA-1 CYTOPLASMIC DOMAIN, The Journal of biological chemistry, 271(28), 1996, pp. 16580-16585
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.