IRON, DTXR, AND THE REGULATION OF DIPHTHERIA-TOXIN EXPRESSION

In recent years considerable advances have been made in the understand ing of the molecular basis of iron-mediated regulation of diphtheria t oxin expression. The fox gene has been shown to be regulated by the he avy metal ion-activated regulatory element DtxR. In the presence of di valent heavy metal ions, DtxR becomes activated and binds to a 9 bp in terrupted palindromic sequence. The consensus-binding site has been de termined by both the sequence analysis of DtxR-responsive operators cl oned from genomic libraries of Corynebacterium diphtheriae as well as by in vitro genetic methods using cyclic amplification of selected tar gets (CASTing). It Is now clear that DtxR functions as a global iron-s ensitive regulatory element in the control of gene expression in C. di phtheriae. In addition, the metal ion-activation domain of DtxR is bei ng characterized by both mutational analysis and determination of the X-ray structure at 3.0 Angstrom resolution.