We have studied the role of the cytoplasmic domain in the conformation and affinity modulation of the integrin β1. Expression of a conformation- dependent anti-β1 antibody 15/7 correlates with activation in wild-type β1. Truncation of 16 carboxyl-terminal residues in the cytoplasmic domain (the 762t β1 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 β1 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 β1 (within residues 354-425). The 762t mutant has apparently normal α/β association, suggesting that the overexpression of the 15/7 epitope is not due to α/β dissociation. The data suggest that the carboxyl-terminal 16 residues of the β1 cytoplasmic domain are critical for properly modulating conformation and affinity of β1 integrins.
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