DesK thermosensing relies on a coiled-coil switch.

ABRIATA, LUCIANO; ALBANESI, DANIELA; SAITA, EMILIO; DE MENDOZA, DIEGO

Congreso; Reunión Conjunta de Sociedades de Biociencias.; 2017

Propagation of a signal through transmembrane segments of a sensor protein is key at the initial stage of many complex signaling processes. 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. Based on structure-guided mutagenesis, we have proposed a mechanism of DesK-mediated signal sensing and transduction. Specifically, 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 favoring such conformational changes. 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. At present, we are dedicating our efforts to crystallize full-length DesK for X-ray structure determination, expecting to shed light on DesK?s transmembrane sensing mechanics.