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.

DesK是一种芽孢杆菌热传感器激酶，在高温下不活跃，但在温度降至25°C以下时又被激活。令人惊讶的是，缺乏跨膜区域的催化结构域（DesKC）在较高温度下更具活性，显示出与DesK有关的反向调控。跨膜区域如何控制催化结构域，在高温下抑制活性，但在较低温度下活化呢？通过设计一组温度最小化的传感器，它们共享相同的催化胞质结构域，但沿跨膜螺旋形成氢键（H键）的残基的数量和位置不同，我们能够调节，反转或断开输入的活动信号。通过支持差分H键网络，可以将激活峰移向更低或更高的温度。该原理可能涉及其他传感器的调节，因为环境物理化学变化或修饰跨膜氢键模式的突变会使平衡倾斜，从而有利于其他构象。