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Structure of the metal-ion-activated diphtheria toxin repressor/ tox operator complex

Nature volume 394, pages 502–506 (1998)Cite this article

Abstract

The virulent phenotype of the pathogenic bacterium Corynebacterium diphtheriae is conferred by diphtheria toxin, whose expression is an adaptive response to low concentrations of iron. The expression of the toxin gene (tox) is regulated by the repressor DtxR (ref. 1), which is activated by transition metal ions. X-ray crystal structures of DtxR with2,3,4,5 and without (apo-form2) 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-triggered subunit–subunit ‘caliper-like’ conformational change. Here we report thethree-dimensional crystal structure of the complex between a biologically active Ni(ii)-bound DtxR(C102D) mutant, in whicha cysteine is replaced by an aspartate at residue 102, and a 33-base-pair DNA segment containing the toxin operator tox O. This structure shows that DNA interacts with two dimeric repressor proteins bound to opposite sides of the tox operator. We propose that a metal-ion-induced helix-to-coil structural transition in the amino-terminal region of the protein is partly responsible for the unique mode of repressor activation by transition metal ions.

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Figure 1: The trans -regulated expression of the diphtheria toxin gene, tox, in C.diphtheriae.
Figure 2: Structure of the Ni(ii)-DtxR(C102D)- tox operator complex.
Figure 3: Repressor–DNA interactions.
Figure 4: Metal-binding sites.

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Acknowledgements

This work was supported by a Public Health Service Grant from the National Institute of Allergy and Infectious Diseases and (in part) by a grant from the Lucille P. Markey Charitable Trust. We thank M. Stanton and Y. Wang for help with data collection, D. Peisach and E. Peisach for rendering images, and N. Schiering, S. Chen and G. A. Petsko for discussion.

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  1. Xiaochun Ding

    Present address: Wadsworth Center, room C160, PO Box 509, Albany, New York, 12201-0509, USA

Authors and Affiliations

  1. Rosenstiel Basic Medical Sciences Research Center MS029,

    André White, Xiaochun Ding & Dagmar Ringe

  2. Departments of Biochemistry and Chemistry, Brandeis Univesity, Waltham, 02454-9110, Massachusetts, USA

    Dagmar Ringe

  3. Department of Medicine, Boston University School of Medicine, Boston, 02118-2393, Massachusetts, USA

    Johanna C. vanderSpek & John R. Murphy

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Correspondence to Dagmar Ringe.

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White, A., Ding, X., vanderSpek, J. et al. Structure of the metal-ion-activated diphtheria toxin repressor/ tox operator complex. Nature 394, 502–506 (1998). https://doi.org/10.1038/28893

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