Protein-glutamate methylesterase/protein-glutamine glutaminase, CheB type (CheB-like)
Type: Family

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 .

This entry represents response regulators involved in chemoreceptor modification. In bacterial chemotaxis, cellular movement is directed in response to chemical gradients. Transmembrane chemoreceptors that sense the stimuli are coupled (via a coupling protein, CheW) with a signal transduction histidine kinase (CheA). CheA phosphorylates response regulators CheB and CheY. Phosphorylated CheY binds to FliM, a component of the flagellar motor switch complex, and modulates the direction of flagellar rotation
. Response regulator CheB (receptor modification enzyme, protein-glutamate methylesterase) modulates the signalling output of the chemotaxis receptors through control of the level of chemoreceptor methylation . Specific glutamyl residues in the transmembrane chemoreceptor cytoplasmic domain are methylated by methyltransferase CheR to form γ-carboxyl glutamyl methyl esters. These esters can be hydrolyzed by methylesterase CheB. Receptor modification resets the signalling states of receptors, allowing for responses to changes in concentration of the chemical stimuli irrespective of their absolute concentrations .

Response regulators of the microbial two-component signal transduction systems typically consist of an N-terminal CheY-like receiver domain and a C-terminal output (usually DNA-binding) domain . In members of this group, the output domain is an enzymatic domain, protein-glutamate methylesterase (demethylase,

). In response to an environmental stimulus, a phosphoryl group is transferred from the His residue of a signal transduction histidine kinase to an Asp residue in the CheY-like receiver domain of the cognate response regulator. Phosphorylation of the receiver domain induces conformational changes that activate an associated output domain. Phosphorylation-induced conformational changes in the response regulator molecule have been demonstrated in direct structural studies . In members of this group, phosphorylation of receiver domain activates the methylesterase , resulting in the subsequent demethylation of the chemoreceptors.

For additional information please see .