CheY-like superfamily

CheY is a member of the response regulator family in bacterial two-component signalling systems, where CheY receives the signal from the sensor partner, usually a histidine protein kinase. Signal transduction involves phosphotransfer, whereby the histidine kinase phosphorylates a conserved aspartate in the response regulator to activate responses to environmental signals [14636076]. CheY is a single domain protein that folds into a compact globular unit with a flavodoxin-like fold consisting of three-layer alpha/beta/alpha sandwich with 21345 beta topology, where the phosphorylation region lies in a cavity.

Other members of the response regulator family contain a CheY-like receiver domain, which is often found N-terminal to a DNA-binding effector domain. Examples include NarL (nitrate/nitrite response regulator), NtrC (nitrogen regulatory protein C), Spo0A and Spo0F (sporulation response) from Bacillus, PhoA and PhoB cyclin-dependent kinases from Aspergillus, among others.

AmiR, the positive regulator of the amidase operon in Psuedomonas, is an unusual member of the bacterial response regulator family; AmiR is able to bind RNA and uses ligand-regulated activation rather than phopho-activation. It has a CheY-like fold at its N-terminus, but contains two subdomains in a C-terminal extension, one forming a coiled-coil and the other a long alpha helix. As such AmiR may represent a new family of RNA-binding response regulators [10508151].

CheY-like domains can be found in other protein families as well. Examples include the receiver domain of the ethylene receptor (ETR1) from Arabidopsis, which is involved in ethylene detection and signal transduction [10647185]; the N-terminal wing' domain of ornithine decarboxylase from Lactobacilli, which catalyses the conversion of ornithine to putrescine at the beginning of the polyamine pathway [10666573]. The N-terminal domain of the circadian clock protein, KaiA, from cyanobacteria, acts as a psuedo-receiver domain, but lacks the conserved aspartyl residue required for phosphotransfer in response regulators [12438647].