Figure 1: The CckA-ChpT-CtrA signalling pathway directly regulates cell cycle progression in Caulobacter crescentus.

(a) The hybrid histidine kinase (HK) CckA authophosphorylates and subsequently transfers the phosphate through the phosphotransfer protein ChpT to the master regulator CtrA (grey box). Through ChpT, CckA is bifunctional as both a kinase and phosphatase of CtrA. Active CtrA∼P (grey shading) regulates the transcription of more than 90 cell cycle regulated genes and inhibits the initiation of DNA replication. On subcellular localization to the old and new cell poles, the sensor histidine kinase CckA (orange) autophosphorylates and thus activates CtrA∼P. Deactivation of CtrA∼P, enabling DNA replication, occurs in early stalked cells and the stalked cell compartment of predivisional cells via two mechanisms: dephosphorylation and proteolysis. (b) A schematic of CckA illustrates its domain architecture and kinase function. The numbered line above CckA indicates residue cutoffs for each of the domains. CckA contains two transmembrane helices at the N-terminus that have been truncated for in vitro experiments. Two unique PAS domains, A and B, comprise an N-terminal sensory region. The catalytic core of CckA features a DHp domain, the site of histidine autophosphorylation and an ATP-binding CA domain. The RD shuttles phosphate from the active site histidine through a conserved aspartate to the downstream phosphorelay protein ChpT. (c) The schematic of CckA illustrates a model for its phosphatase function. Phosphate can be removed from the conserved aspartate in the RD, allowing CckA to act as a phosphatase for the CtrA pathway. A conserved DxxN residue motif adjacent to the conserved phosphorylatable histidine in the DHp domain assists in catalysis.