Driving the catalytic activity of a transmembrane thermosensor kinase


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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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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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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  • Signal transduction
  • Transmembrane signalling
  • Histidine kinase
  • Cold adaptation
  • Dimerization motif
  • Activity regulation
  • Receptor