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Driving the catalytic activity of a transmembrane thermosensor kinase

  • María Eugenia Inda
  • Juan Cruz Almada
  • Daniela Belén Vazquez
  • Ana Bortolotti
  • Ariel Fernández
  • Jean Marie Ruysschaert
  • Larisa Estefanía CybulskiEmail author
Original Article
  • 29 Downloads

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.

Keywords

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

Notes

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.

Author 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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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • María Eugenia Inda
    • 1
  • Juan Cruz Almada
    • 1
  • Daniela Belén Vazquez
    • 1
  • Ana Bortolotti
    • 1
  • Ariel Fernández
    • 2
    • 3
  • Jean Marie Ruysschaert
    • 4
  • Larisa Estefanía Cybulski
    • 1
    Email author
  1. 1.Departamento de Microbiología, Facultad de Ciencias Bioquímicas y FarmacéuticasUniversidad Nacional de Rosario-Argentine National Research Council-CONICETRosarioArgentina
  2. 2.Argentine Mathematics Institute-IAM/CONICETBuenos AiresArgentina
  3. 3.Chemistry Institute-INQUISUR/UNS, National Research Council-CONICETBahía BlancaArgentina
  4. 4.Structure et Fonction des Membranes Biologiques (SFMB) Campus de la PlaineBoulevard du TriompheBrusselsBelgium

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