Iron, DtxR, and the regulation of diphtheria toxin expression |
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Authors: | Xu Tao Nikolaus Schiering Hui-yan Zeng Dagmar Ringe John R Murphy |
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Institution: | Evans Department of Clinical Research and Department of Medicine, Boston University Medical Center Hospital, Boston, Massachusetts 02118, USA.;Departments of Biochemistry and Chemistry, Brandeis University, Waltham, Massachusetts 02254, USA. |
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Abstract: | In recent years considerable advances have been made in the understanding of the molecular basis of iron-mediated regulation of diphtheria toxin expression. The tox gene has been shown to be regulated by the heavy metal ion-activated regulatory element DtxR. In the presence of divalent heavy metal ions, DtxR becomes activated and binds to a 9 bp interrupted palindromic sequence. The consensus-binding site has been determined by both the sequence analysis of DtxR-responsive operators cloned from genomic libraries of Corynebacterium diphtheriae as well as by in vitro genetic methods using cyclic amplification of selected targets (CAST-ing). it is now clear that DtxR functions as a global iron-sensitive regulatory element in the control of gene expression in C. diphtheriae. In addition, the metal ion-activation domain of DtxR is being characterized by both mutational analysis and determination of the X-ray structure at 3.0 Å resolution. |
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