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Driving the catalytic activity of a transmembrane thermosensor kinase

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Abstract

DesK is a Bacillus thermosensor kinase that is inactive at high temperatures but turns activated when the temperature drops below 25 °C. Surprisingly, the catalytic domain (DesKC) lacking the transmembrane region is more active at higher temperature, showing an inverted regulation regarding DesK. How does the transmembrane region control the catalytic domain, repressing activity at high temperatures, but allowing activation at lower temperatures? By designing a set of temperature minimized sensors that share the same catalytic cytoplasmic domain but differ in number and position of hydrogen-bond (H-bond) forming residues along the transmembrane helix, we are able to tune, invert or disconnect activity from the input signal. By favoring differential H-bond networks, the activation peak could be moved towards lower or higher temperatures. This principle may be involved in regulation of other sensors as environmental physicochemical changes or mutations that modify the transmembrane H-bond pattern can tilt the equilibrium favoring alternative conformations.

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Acknowledgements

This work was supported by Grants from Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Agencia Nacional de Promoción Científica y Tecnológica (FONCYT), and international cooperations: CONICET-Fonds National de la Recherche Scientifique (FNRS). M.E.I., J.C.A and D.B.V are Fellows of CONICET, and L.E.C., A.B. and A.F. are Career Investigators of CONICET.

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Author notes

  1. María Eugenia Inda and Juan Cruz Almada contributed equally.

Authors and Affiliations

  1. Departamento de Microbiología, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario-Argentine National Research Council-CONICET, Suipacha 531, 2000, Rosario, Argentina

    María Eugenia Inda, Juan Cruz Almada, Daniela Belén Vazquez, Ana Bortolotti & Larisa Estefanía Cybulski

  2. Argentine Mathematics Institute-IAM/CONICET, 1053, Buenos Aires, Argentina

    Ariel Fernández

  3. Chemistry Institute-INQUISUR/UNS, National Research Council-CONICET, 8000, Bahía Blanca, Argentina

    Ariel Fernández

  4. Structure et Fonction des Membranes Biologiques (SFMB) Campus de la Plaine, Boulevard du Triomphe, CP206/02, 1050, Brussels, Belgium

    Jean Marie Ruysschaert

Authors
  1. María Eugenia Inda
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  2. Juan Cruz Almada
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  3. Daniela Belén Vazquez
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  4. Ana Bortolotti
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  5. Ariel Fernández
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  6. Jean Marie Ruysschaert
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  7. Larisa Estefanía Cybulski
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Contributions

MEI, DBV, AB and JCA performed the experiments and discussed the results. LEC envisioned and coordinated the project and wrote the manuscript. JMR, AF and MEI contributed to the writing.

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Correspondence to Larisa Estefanía Cybulski.

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Inda, M.E., Almada, J.C., Vazquez, D.B. et al. Driving the catalytic activity of a transmembrane thermosensor kinase. Cell. Mol. Life Sci. 77, 3905–3912 (2020). https://doi.org/10.1007/s00018-019-03400-1

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  • DOI: https://doi.org/10.1007/s00018-019-03400-1

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