F
IPR008248

Protein-glutamate methylesterase/protein-glutamine glutaminase, CheB type

InterPro entry
Short nameCheB-like
Overlapping
homologous
superfamilies
 

Description

Two-component signal transduction systems enable bacteria to sense, respond, and adapt to a wide range of environments, stressors, and growth conditions
[11]
. Some bacteria can contain up to as many as 200 two-component systems that need tight regulation to prevent unwanted cross-talk
[12]
. 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
[13]
. Two-component systems are comprised of a sensor histidine kinase (HK) and its cognate response regulator (RR)
[2]
. 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
[14, 15]
.

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
[1]
. 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
[1]
. 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
[1]
.

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
[2, 3]
. In members of this group, the output domain is an enzymatic domain, protein-glutamate methylesterase (demethylase,
3.1.1.61
). 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
[4]
. In members of this group, phosphorylation of receiver domain activates the methylesterase
[5]
, resulting in the subsequent demethylation of the chemoreceptors.

For additional information please see
[6, 7, 8, 9, 10]
.

References

1.Structural analysis of bacterial chemotaxis proteins: components of a dynamic signaling system. Djordjevic S, Stock AM. J. Struct. Biol. 124, 189-200, (1998). View articlePMID: 10049806

2.Two-component signal transduction. Stock AM, Robinson VL, Goudreau PN. Annu. Rev. Biochem. 69, 183-215, (2000). View articlePMID: 10966457

3.Histidine kinases and response regulator proteins in two-component signaling systems. West AH, Stock AM. Trends Biochem. Sci. 26, 369-76, (2001). View articlePMID: 11406410

4.Dimer formation and transcription activation in the sporulation response regulator Spo0A. Lewis RJ, Scott DJ, Brannigan JA, Ladds JC, Cervin MA, Spiegelman GB, Hoggett JG, Barak I, Wilkinson AJ. J. Mol. Biol. 316, 235-45, (2002). View articlePMID: 11851334

5.Phosphorylation of an N-terminal regulatory domain activates the CheB methylesterase in bacterial chemotaxis. Lupas A, Stock J. J. Biol. Chem. 264, 17337-42, (1989). View articlePMID: 2677005

6.The two-component signaling pathway of bacterial chemotaxis: a molecular view of signal transduction by receptors, kinases, and adaptation enzymes. Falke JJ, Bass RB, Butler SL, Chervitz SA, Danielson MA. Annu. Rev. Cell Dev. Biol. 13, 457-512, (1997). View articlePMID: 9442881

7.Activation of methylesterase CheB: evidence of a dual role for the regulatory domain. Anand GS, Goudreau PN, Stock AM. Biochemistry 37, 14038-47, (1998). View articlePMID: 9760239

8.Allosteric enhancement of adaptational demethylation by a carboxyl-terminal sequence on chemoreceptors. Barnakov AN, Barnakova LA, Hazelbauer GL. J. Biol. Chem. 277, 42151-6, (2002). View articlePMID: 12196531

9.Mind your B's and R's: bacterial chemotaxis, signal transduction and protein recognition. Jurica MS, Stoddard BL. Structure 6, 809-13, (1998). View articlePMID: 9687374

10.Structural conservation in the CheY superfamily. Volz K. Biochemistry 32, 11741-53, (1993). View articlePMID: 8218244

11.Two-component signal transduction pathways regulating growth and cell cycle progression in a bacterium: a system-level analysis. Skerker JM, Prasol MS, Perchuk BS, Biondi EG, Laub MT. PLoS Biol. 3, e334, (2005). View articlePMID: 16176121

12.Specificity in two-component signal transduction pathways. Laub MT, Goulian M. Annu. Rev. Genet. 41, 121-45, (2007). View articlePMID: 18076326

13.Histidine protein kinases: key signal transducers outside the animal kingdom. Wolanin PM, Thomason PA, Stock JB. Genome Biol. 3, REVIEWS3013, (2002). View articlePMID: 12372152

14.Molecular recognition of bacterial phosphorelay proteins. Varughese KI. Curr. Opin. Microbiol. 5, 142-8, (2002). View articlePMID: 11934609

15.Keeping signals straight in phosphorelay signal transduction. Hoch JA, Varughese KI. J. Bacteriol. 183, 4941-9, (2001). View articlePMID: 11489844

GO terms

Cross References

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