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Mol Microbiol. 2015 Oct;98(2):258-71. doi: 10.1111/mmi.13118. Epub 2015 Aug 3.

A coiled coil switch mediates cold sensing by the thermosensory protein DesK.

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Laboratorio de Fisiología Microbiana, Instituto de Biología Molecular y Celular de Rosario (IBR), CONICET, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Ocampo y Esmeralda, Predio CONICET Rosario, 2000, Rosario, Argentina.
Laboratory for Biomolecular Modeling, School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), Swiss Institute of Bioinformatics (SIB), AAB011 Station 19, 1015, Lausanne, Switzerland.
Institut Pasteur de Montevideo, Unit of Protein Crystallography, Mataojo 2020, Montevideo, 11400, Uruguay.
Département de Biologie Structurale et Chimie, Institut Pasteur, 25 rue du Dr. Roux, Paris, 75015, France.


The thermosensor histidine kinase DesK from Bacillus subtilis senses changes in membrane fluidity initiating an adaptive response. Structural changes in DesK have been implicated in transmembrane signaling, but direct evidence is still lacking. On the basis of structure-guided mutagenesis, we now propose a mechanism of DesK-mediated signal sensing and transduction. The data indicate that stabilization/destabilization of a 2-helix coiled coil, which connects the transmembrane sensory domain of DesK to its cytosolic catalytic region, is crucial to control its signaling state. Computational modeling and simulations reveal couplings between protein, water and membrane mechanics. We propose that membrane thickening is the main driving force for signal sensing and that it acts by inducing helix stretching and rotation prompting an asymmetric kinase-competent state. Overall, the known structural changes of the sensor kinase, as well as further dynamic rearrangements that we now predict, consistently link structure determinants to activity modulation.

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