Multiple disordered loops function in corepressor-induced dimerization of the biotin repressor

Cooperative association of the Escherichia coli biotin repressor with the b iotin operator is allosterically activated by binding of the corepressor, b io-5'-AMP. The corepressor function of the adenylate is due, in part, to it s ability to induce repressor dimerization. Since a high-resolution structu re of only the apo or unliganded repressor is currently available, the loca tion of the dimerization interface on the protein structure is not known. H ere, five mutants in the corepressor-binding domain of the repressor have b een analyzed with respect to their DNA-binding and self-assembly properties . Results of these studies reveal that four of the mutant proteins exhibit defects in DNA binding. These same proteins are compromised in self-assembl y. Furthermore, in the three-dimensional structure of the apo protein the m utations all lie in partially disordered surface loops, one of which is kno wn to participate directly in corepressor binding. These results suggest th at multiple disordered surface loops function in the corepressor-induced di merization required for sequence-specific DNA binding by the biotin repress or. (C) 2000 Academic Press.