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Structural insights into the signalling mechanisms of two-component systems

Nature Reviews Microbiology volume 16, pages 585–593 (2018)Cite this article

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Abstract

Two-component systems reprogramme diverse aspects of microbial physiology in response to environmental cues. Canonical systems are composed of a transmembrane sensor histidine kinase and its cognate response regulator. They catalyse three reactions: autophosphorylation of the histidine kinase, transfer of the phosphoryl group to the regulator and dephosphorylation of the phosphoregulator. Elucidating signal transduction between sensor and output domains is highly challenging given the size, flexibility and dynamics of histidine kinases. However, recent structural work has provided snapshots of the catalytic mechanisms of the three enzymatic reactions and described the conformation and dynamics of the enzymatic moiety in the kinase-competent and phosphatase-competent states. Insight into signalling mechanisms across the membrane is also starting to emerge from new crystal structures encompassing both sensor and transducer domains of sensor histidine kinases. In this Progress article, we highlight such important advances towards understanding at the molecular level the signal transduction mechanisms mediated by these fascinating molecular machines.

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Fig. 1: Architectures of two-component systems and of sensor kinases.
Fig. 2: The kinase and phosphatase states.
Fig. 3: Sensing and signalling by SHKs.

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Acknowledgements

The authors thank E. Pradel for carefully reading the manuscript. They also thank A. Buschiazzo, F. Trajtenberg and J. Imelio (Institut Pasteur of Montevideo) for kindly sharing the coordinates file of the DesK–DesR complex model shown in Fig. 2a. The work in F.J.-D.’s group was supported by the Agence Nationale de la Recherche (grant ANR-10-BLAN-1306). The authors apologize to all colleagues whose excellent work on two-component systems could not be cited because of space limitations.

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Nature Reviews Microbiology thanks V. Gordeliy and A. Möglich and the other anonymous reviewer(s) for their contribution to the peer review of this work.

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Authors and Affiliations

  1. Université de Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019-UMR 8204 – Center for Infection and Immunity of Lille, Lille, France

    Françoise Jacob-Dubuisson & Rudy Antoine

  2. Institut Pasteur, Plateforme de Cristallographie, CNRS-UMR3528, Paris, France

    Ariel Mechaly

  3. Institut Pasteur, Unité de Microbiologie Structurale, CNRS-UMR3528, Paris, France

    Jean-Michel Betton

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F.J.-D., A.M., J.-M.B. and R.A. researched data for the article and made substantial contributions to discussions of the content. F.J.-D., J.-M.B. and A.M. wrote the article. F.J.-D., A.M. and R.A. reviewed and/or edited the manuscript before submission.

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Jacob-Dubuisson, F., Mechaly, A., Betton, JM. et al. Structural insights into the signalling mechanisms of two-component systems. Nat Rev Microbiol 16, 585–593 (2018). https://doi.org/10.1038/s41579-018-0055-7

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