XrtA/PEP-CTERM system histidine kinase PrsK (XrtA/PrsK)
Type: Family

Proteins in this entry have a novel N-terminal domain, a single predicted membrane-spanning helix, and a predicted cytosolic histidine kinase domain. It was designated PrsK, and its companion DNA-binding response regulator protein (

) PrsR. These predicted signal-transducing proteins appear to enable enhancer-dependent transcriptional activation. The prsK gene is often associated with exopolysaccharide biosynthesis genes . They all contain a GAF domain that is present in phytochromes and cGMP-specific phosphodiesterases, and which has been experimentally proven to be involved in protein:protein interactions. They also contain a C-terminal histidine kinase domain, which is composed of a dimerisation sub-domain and an ATP/ADP-binding phosphotransfer, or catalytic, sub-domain. The proteins in this entry are found strictly within a subset of Gram-negative bacterial species with the proposed PEP-CTERM/exosortase system, analogous to the LPXTG/sortase system common in Gram-positive bacteria, where members of

and

also occur.

This family also includes the putative exosortase XrtA (previously called EpsH). which cleaves the PEP-CTERM .

Signal transducing histidine kinases are the key elements in two-component signal transduction systems, which control complex processes such as the initiation of development in microorganisms . Examples of histidine kinases are EnvZ, which plays a central role in osmoregulation , and CheA, which plays a central role in the chemotaxis system . Histidine kinases usually have an N-terminal ligand-binding domain and a C-terminal kinase domain, but other domains may also be present. The kinase domain is responsible for the autophosphorylation of the histidine with ATP, the phosphotransfer from the kinase to an aspartate of the response regulator, and (with bifunctional enzymes) the phosphotransfer from aspartyl phosphate back to ADP or to water . The kinase core has a unique fold, distinct from that of the Ser/Thr/Tyr kinase superfamily.

Two-component signal transduction systems enable bacteria to sense, respond, and adapt to a wide range of environments, stressors, and growth conditions . Some bacteria can contain up to as many as 200 two-component systems that need tight regulation to prevent unwanted cross-talk . These pathways have been adapted to response to a wide variety of stimuli, including nutrients, cellular redox state, changes in osmolarity, quorum signals, antibiotics, and more . Two-component systems are comprised of a sensor histidine kinase (HK) and its cognate response regulator (RR) . The HK catalyses its own auto-phosphorylation followed by the transfer of the phosphoryl group to the receiver domain on RR; phosphorylation of the RR usually activates an attached output domain, which can then effect changes in cellular physiology, often by regulating gene expression. Some HK are bifunctional, catalysing both the phosphorylation and dephosphorylation of their cognate RR. The input stimuli can regulate either the kinase or phosphatase activity of the bifunctional HK.

A variant of the two-component system is the phospho-relay system. Here a hybrid HK auto-phosphorylates and then transfers the phosphoryl group to an internal receiver domain, rather than to a separate RR protein. The phosphoryl group is then shuttled to histidine phosphotransferase (HPT) and subsequently to a terminal RR, which can evoke the desired response .