Sensory kinase KdpD is a tandem serine histidine kinase controlling K⁺pump KdpFABC on the translational and post-transcriptional level

Abstract

Two-component systems (TCSs), consisting of a histidine kinase (HK) and a response regulator, serve signal transduction in bacteria, often regulating transcription in response to environmental stimuli. Here, we identify a tandem serine histidine kinase function for KdpD, previously described as a HK of the TCS KdpDE, which controls production of the K+pump KdpFABC. We show that KdpD additionally mediates an inhibitory serine phosphorylation of KdpFABC at high K+levels, using not its C-terminal HK domain but an N-terminal atypical serine kinase (ASK) domain. Sequence analysis of KdpDs from different species highlights that some KdpDs comprise solely ASK and Usp domains. We show that, whileEscherichia coliKdpD’s ASK responds directly to K+levels, a shorter version fromDeinococcus geothermalisis controlled by second messenger cyclic di-AMP. Our findings add to the growing functional diversity of sensor kinases while simultaneously expanding the framework for regulatory mechanisms in bacterial K+homeostasis.

Regulation of potassium homeostasis inCaulobacter crescentus

“…Therefore, it is possible that such a connection between intracellular sensing and phosphatase activity does not exist in C. crescentus, which would explain why KdpD mainly acts as a phosphatase. Recently, it was reported that E. coli KdpD also works as serine kinase in high K + concentrations to control KdpB ATPase activity and ultimately stop Kdp-dependent K + transport (57). The phosphorylated serine residue in KdpB as well as the two Walker (A and B) domains in tandem driving the serine kinase activity of KdpD are highly conserved in C. crescentus (Fig.…”