Driving the catalytic activity of a transmembrane thermosensor kinase
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Cellular and Molecular Life Sciences
ORIGINAL ARTICLE
Driving the catalytic activity of a transmembrane thermosensor kinase María Eugenia Inda1 · Juan Cruz Almada1 · Daniela Belén Vazquez1 · Ana Bortolotti1 · Ariel Fernández2,3 · Jean Marie Ruysschaert4 · Larisa Estefanía Cybulski1 Received: 22 August 2019 / Revised: 6 November 2019 / Accepted: 26 November 2019 © Springer Nature Switzerland AG 2019
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
Introduction Transmembrane sensors and receptors are informant proteins that communicate the cell what is going on in its environment. In the mesophilic bacterium Bacillus subtilis, the transmembrane sensor DesK triggers a cellular response to overcome membrane rigidity when temperature decreases. At optimal growth temperature (~ 37 °C), DesK is inactive as kinase. At sub-optimal growth temperatures (25 °C, [1, 2]), María Eugenia Inda and Juan Cruz Almada contributed equally. * Larisa Estefanía Cybulski [email protected] 1
Departamento de Microbiología, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario-Argentine National Research Council-CONICET, Suipacha 531, 2000 Rosario, Argentina
2
Argentine Mathematics Institute-IAM/CONICET, 1053 Buenos Aires, Argentina
3
Chemistry Institute-INQUISUR/UNS, National Research Council-CONICET, 8000 Bahía Blanca, Argentina
4
Structure et Fonction des Membranes Biologiques (SFMB) Campus de la Plaine, Boulevard du Triomphe, CP206/02, 1050 Brussels, Belgium
the lipids pack together and the membrane becomes thicker, promoting the kinase state of DesK. Then DesK phosphorylates the response regulator DesR, which in turn activates the downstream circuit to optimize the performance of many cellular physiological processes at the new temperature (Fig. 1a, [3–5]). For optimal performance, membrane enzymes need a fluid bilayer and kin
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