STRUCTURE OF THE METAL-ION-ACTIVATED DIPHTHERIA-TOXIN-REPRESSOR TOX-OPERATOR COMPLEX

The virulent phenotype of the pathogenic bacterium Corynebacterium dip htheriae is conferred by diphtheria toxin, whose expression is an adap tive response to low concentrations of iron. The expression of the tox in gene (tox) is regulated by the repressor DtxR (ref. 1), which is ac tivated by transition metal ions. X-ray crystal structures of DtxR wit h(2-5) and without (apo-form(2)) its coordinated transition metal ion have established the general architecture of the repressor, identified the location of the metal-binding sites, and revealed a metal-ion-tri ggered subunit-subunit 'caliper-like' conformational change, Here we r eport the three-dimensional crystal structure of the complex between a biologically active Ni(II)-bound DtxR(C102D) mutant, in which a cyste ine is replaced by an aspartate at residue 102, and a 33-base-pair DNA segment containing the toxin operator toxO. This structure shows that DNA interacts with two dimeric repressor proteins bound to opposite s ides of the tox operator. We propose that a metal-ion-induced helix-to -coil structural transition in the amino-terminal region of the protei n is partly responsible for the unique mode of repressor activation by transition metal ions.