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The structure of a protein bound to DNA reveals how the toxicity of the cholera bacterium is activated

    A team led by Dr. Miquel Coll, at the Institute of Molecular Biology of Barcelona (IBMB-CSIC) and the Institute for Research in Biomedicine (IRB Barcelona), in collaboration with researchers led by Dr. Eric Krukonis at the University of Detroit Mercy in the USA, has revealed the atomic structure of the ToxR protein bound to the DNA of two promoters of the genes that cause the virulence of Vibrio cholerae. The study has been published in the journal PNAS.


    ToxR, a Vibrio cholerae transmembrane one-component signal transduction factor, lies within a regulatory cascade that results in the expression of ToxT, toxin coregulated pilus, and cholera toxin. While ToxR has been extensively studied for its ability to activate or repress various genes in V. cholerae, this work presents the crystal structures of the ToxR cytoplasmic domain bound to DNA at the toxT and ompU promoters. The structures confirm some predicted interactions, yet reveal other unexpected promoter interactions with implications for other potential regulatory roles for ToxR. ToxR is a versatile virulence regulator that recognizes diverse and extensive, eukaryotic-like regulatory DNA sequences, and that relies more on DNA structural elements than specific sequences for binding. Using this topological DNA recognition mechanism, ToxR can bind both in tandem and in a twofold inverted-repeat-driven manner. Its regulatory action is based on coordinated multiple binding to promoter regions near the transcription start site, which can remove the repressing H-NS proteins and prepares the DNA for optimal interaction with the RNA polymerase.


    Canals A, Pieretti S, Muriel-Masanes M, El Yaman N, Plecha SC, Thomson JJ, Fàbrega-Ferrer M, Pérez-Luque R, Krukonis ES, Coll M. ToxR activates the Vibrio cholerae virulence genes by tethering DNA to the membrane through versatile binding to multiple sites. Proc Natl Acad Sci U S A. 2023 Jul 18;120(29):e2304378120. doi: 10.1073/pnas.2304378120. Epub 2023 Jul 10. PMID: 37428913.

    Atomic three-dimensional model showing several ToxR proteins bound to DNA.
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