A Transmembrane Histidine Kinase Functions as a pH Sensor.

The two-component system DesK-DesR regulates the synthesis of unsaturated fatty acids in the soil bacteria . This system is activated at low temperature and maintains membrane lipid fluidity upon temperature variations. Here, we found that DesK-the transmembrane histidine kinase-also responds to pH and studied the mechanism of pH sensing.

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.

Reverse Engineering of a Thermosensing Regulator Switch.

To address the mechanism of thermosensing and its implications for molecular engineering, we previously deconstructed the functional components of the bacterial thermosensor DesK, a histidine kinase with a five-span transmembrane domain that detects temperature changes. The system was first simplified by building a sensor that consists of a single chimerical transmembrane segment that retained full sensing capacity. Genetic and biophysical analysis of this minimal sensor enabled the identification of three modular components named determinants of thermodetection (DOTs).

Activation of the bacterial thermosensor DesK involves a serine zipper dimerization motif that is modulated by bilayer thickness.

DesK is a bacterial thermosensor protein involved in maintaining membrane fluidity in response to changes in environmental temperature. Most likely, the protein is activated by changes in membrane thickness, but the molecular mechanism of sensing and signaling is still poorly understood. Here we aimed to elucidate the mode of action of DesK by studying the so-called "minimal sensor DesK" (MS-DesK), in which sensing and signaling are captured in a single transmembrane segment.