InterPro

Two-component signal transduction systems enable bacteria to sense, respond, and adapt to a wide range of environments, stressors, and growth conditions [PMID: 16176121]. Some bacteria can contain up to as many as 200 two-component systems that need tight regulation to prevent unwanted cross-talk [PMID: 18076326]. 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 [PMID: 12372152]. Two-component systems are comprised of a sensor histidine kinase (HK) and its cognate response regulator (RR) [PMID: 10966457]. 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 [PMID: 11934609, PMID: 11489844].

This entry represents a structural domain usually found at the C-terminal of bipartite response regulators. These proteins are known to bind to DNA and RNA polymerases, and their N-terminal receiver domain belongs to the CheY family. The C-terminal effector domain consists of a 3-helical bundle in an up-an-down arrangement with a right-handed twist. This domain occurs in:

• PhoB-like proteins, which includes PhoB [PMID: 12015152], OmpR [PMID: 8989318], and DrrB [PMID: 12837793]; these proteins contain a 4-stranded meander beta-sheet in the N-terminal extension.
• GerE-like proteins from the LuxR/UhpA family of proteins, which includes GerE [PMID: 11243786], TraR (quorum-sensing) [PMID: 12198141], NarL (nitrate/nitrite response regulator) [PMID: 9521685], and RcsB transcriptional regulator [PMID: 12740396]; these proteins contain an additional fourth helix in the C-terminal extension.
• Spo0A proteins [PMID: 11069648], which are elaborated with additional helices.