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Escherichia coli K-12 substr. MG1655 Protein: CheA(L) histidine kinase



Gene: cheA Accession Numbers: EG10146 (EcoCyc), b1888, ECK1889

Synonyms: chemotaxis kinase-phosphotransferase CheA(L)

Regulation Summary Diagram: ?

Component of:
chemotaxis signaling complex - ribose/galactose/glucose sensing (extended summary available)
chemotaxis signaling complex - dipeptide sensing (extended summary available)
chemotaxis signaling complex - serine sensing (extended summary available)
chemotaxis signaling complex - aspartate sensing (extended summary available)

Subunit composition of CheA(L) histidine kinase = [CheA]2

Alternative forms of CheA: CheA(L) sensory histidine kinase - phosphorylated (summary available)

Alternative forms of chemotaxis signaling complex - ribose/galactose/glucose sensing:
Trgglu-Me
Trgglu
Trggln

Alternative forms of chemotaxis signaling complex - dipeptide sensing:
Tapglu-Me
Tapglu
Tapgln

Alternative forms of chemotaxis signaling complex - serine sensing:
Tsrglu-Me
Tsrglu
Tsrgln (extended summary available)

Alternative forms of chemotaxis signaling complex - aspartate sensing:
Targlu-Me
Targlu
Targln

Summary:
CheA is the histidine kinase component of the chemotaxis two-component signal transduction complex. The chemotaxis system propagates changes in extracellular chemical concentrations to the flagellar switch complex to regulate swimming behavior. CheA and CheY comprise a two-component signal transduction system where the signal generated by the periplasmic receptor occupancy through a protein-protein interaction with the CheA cytoplasmic component is transmitted via phosphorylation from autophosphorylating histidine kinase CheA to CheY (the response regulator) [Welch93]. The receptor complexes (MCPI, MCPII, MCPIII and MCPIV) are ternary structures consisting of receptors, CheA and the adaptor protein CheW.

Escherichia coli expresses CheA as both a full length molecule as well as a shorter version translated from an alternative start codon known as CheA(short), which contains a catalytic domain but no kinase substrate domain [Kofoid91]. As a result, a heterodimer containing a full-length CheA alongside a CheA(s) exhibits a fivefold higher autophosphorylation rate than the CheA homodimer [Levit96].

CheA autophosphorylates on His48 in the presence of ATP in vitro. The phosphate group on CheA can be transferred to CheB or to CheY in vitro [Hess88, Hess88a]. CheA is a dimer in solution. Two CheW monomers bind per CheA dimer [Gegner91]. CheA autophosphorylation results from transphosphorylation within the dimer [Swanson93]. In an in vitro reconstituted system, autophosphorylation of purified CheA is stimulated by addition of wild type Tar receptor and CheW protein [Borkovich90, Borkovich89]. CheA contains separate functional domains associated with kinase activity, CheY binding, phosphotransfer activity and receptor binding [Swanson93a, Bourret93, Morrison94, Stewart00, Stewart04, Bhatnagar12]. CheA interacts with chemoreceptors in a manner similar to CheW; CheA and CheW bind to the same region of chemoreceptors due to structural similarity between CheW and the regulatory or P5 domain of CheA [Wang12a]. Chemotaxis receptors control kinase activity by regulating CheA domain mobility [Briegel13].
The cheA gene is translated in two isoforms. The small form, CheA(S), arises due to a second translational start site 291 bases downstream of the translation start site for the large form, CheA(L) [Hoch95, Neidhardt96].

The "Spliced Nucleotide Sequence" link above refers to the smaller variant, but note that no splicing occurs.

Citations: [Zhao06, Levit02, Francis04, Morrison97, Piasta13, Garzon96, Thakor11]

Gene Citations: [Silverman77, Mirel92]

Locations: inner membrane, cytosol

Map Position: [1,971,384 <- 1,973,348] (42.49 centisomes)
Length: 1965 bp / 654 aa

Molecular Weight of Polypeptide: 71.382 kD (from nucleotide sequence)

pI: 4.96

Unification Links: ASAP:ABE-0006294 , CGSC:928 , EchoBASE:EB0144 , EcoGene:EG10146 , EcoliWiki:b1888 , ModBase:P07363 , OU-Microarray:b1888 , PortEco:cheA , RegulonDB:EG10146 , Swiss-Model:P07363

Relationship Links: UniProt:RELATED-TO:P07363

In Paralogous Gene Group: 122 (29 members)

Reactions known to consume the compound:

Aerotactic Two-Component Signal Transduction System , Chemotactic Two-Component Signal Transduction :
CheA + ATP → CheA-P + ADP

Reactions known to produce the compound:

Aerotactic Two-Component Signal Transduction System :
CheY + CheA-P → CheY-Pasp + CheA

Chemotactic Two-Component Signal Transduction :
CheA-P + CheB → CheA + CheB-Pasp
CheY + CheA-P → CheY-Pasp + CheA

Gene-Reaction Schematic: ?

Genetic Regulation Schematic: ?

GO Terms:

Biological Process: GO:0000160 - phosphorelay signal transduction system Inferred from experiment Inferred by computational analysis [UniProtGOA11, GOA01, Igo89]
GO:0016310 - phosphorylation Inferred from experiment Inferred by computational analysis [UniProtGOA11, GOA01, Igo89]
GO:0031400 - negative regulation of protein modification process Inferred from experiment [Barak04]
GO:0046777 - protein autophosphorylation Inferred from experiment [Igo89]
GO:0006935 - chemotaxis Inferred by computational analysis [UniProtGOA11, GOA01]
GO:0007165 - signal transduction Inferred by computational analysis [GOA01]
GO:0018106 - peptidyl-histidine phosphorylation Inferred by computational analysis [GOA01a, GOA01]
GO:0023014 - signal transduction by phosphorylation Inferred by computational analysis [GOA01]
Molecular Function: GO:0005515 - protein binding Inferred from experiment [Thakor11, Rajagopala09, OConnor09, Hao09]
GO:0000155 - phosphorelay sensor kinase activity Inferred by computational analysis [GOA01]
GO:0000166 - nucleotide binding Inferred by computational analysis [UniProtGOA11]
GO:0004673 - protein histidine kinase activity Inferred by computational analysis [GOA01a]
GO:0004871 - signal transducer activity Inferred by computational analysis [GOA01]
GO:0005524 - ATP binding Inferred by computational analysis [UniProtGOA11]
GO:0016301 - kinase activity Inferred by computational analysis [UniProtGOA11]
GO:0016740 - transferase activity Inferred by computational analysis [UniProtGOA11]
GO:0016772 - transferase activity, transferring phosphorus-containing groups Inferred by computational analysis [GOA01]
Cellular Component: GO:0005829 - cytosol Inferred from experiment [Ridgway77]
GO:0005886 - plasma membrane Inferred from experiment [Ridgway77]
GO:0005622 - intracellular Inferred by computational analysis [GOA01]
GO:0005737 - cytoplasm Inferred by computational analysis [UniProtGOA11a, UniProtGOA11, GOA01]

MultiFun Terms: cell processes motility, chemotaxis, energytaxis (aerotaxis, redoxtaxis etc)
information transfer protein related posttranslational modification

Essentiality data for cheA knockouts: ?

Growth Medium Growth? T (°C) O2 pH Osm/L Growth Observations
LB enriched Yes 37 Aerobic 6.95   Yes [Gerdes03, Comment 1]
LB Lennox Yes 37 Aerobic 7   Yes [Baba06, Comment 2]
M9 medium with 1% glycerol Yes 37 Aerobic 7.2 0.35 Yes [Joyce06, Comment 3]
MOPS medium with 0.4% glucose Yes 37 Aerobic 7.2 0.22 Yes [Baba06, Comment 2]

Credits:
Last-Curated ? 06-Aug-2013 by Mackie A , Macquarie University


Subunit of: chemotaxis signaling complex - ribose/galactose/glucose sensing

Synonyms: MCP-III signaling complex

Subunit composition of chemotaxis signaling complex - ribose/galactose/glucose sensing = [(CheA)2][CheW]2[(Trg)2]3
         CheA(L) histidine kinase = (CheA)2
         methyl accepting chemotaxis protein - ribose/galactose/glucose sensing = (Trg)2 (extended summary available)

Summary:
Chemotaxis in Escherichia coli is accomplished with a modified two-component signal transduction complex which transmits controlling signals to the flagellar motor complex. E.coli has four methyl-accepting chemotaxis protein (MCP)-type receptor complexes which recognize the following ligands: Tsr, serine;Tar, aspartate and maltose;Trg, ribose, galactose and glucose and Tap, dipeptides. Serine and aspartate bind directly to the receptor whereas maltose, ribose, galactose, glucose and dipeptides bind first to a periplasmic binding protein which then docks with its individual membrane receptor [Manson98].

The receptor complexes are ternary structures. The receptor-ligand interaction domain is located in the periplasm. Each receptor serves as the organizational framework for a receptor kinase signaling supermolecular complex formed in conjunction with histidine kinase CheA and other components of the signaling pathway [Falke97]. There are two transmembrane (TM) linker domains (CheW) which couple the methylation-dependent receptor to CheA. The receptors form homodimers with or without ligands [Gegner92]. CheA is a histidine kinase capable of autophosphorylation using ATP as a phosphodonor. The receptor complex dimers form trigonal units which in turn form a two-dimensional hexagonal lattice [Shimizu00] located usually at one pole of the cell. The Tsr and Tar receptors are the most abundant and the Tap, Trg receptors are less prevalent [Bren00].

CheA and CheY comprise a two-component signal transduction system where the signal is transmitted via phosphorylation from CheA to CheY (the response regulator). In several ways CheA/CheY differs from the standard two-component paradigm. Most significantly, CheY does not possess a DNA-binding domain and it doesn't act as a transcription factor. In the absence of activator ligand, CheA autophosphorylation is stimulated thus increasing the phosphotransfer from CheA to CheY, the messenger protein. CheY-P has a lower affinity for CheA than CheY, resulting in the dissociation of CheY-P from CheA. CheY-P has a higher affinity than CheY for the flagellar motor protein, FliM, a component of the motor supramolecular complex [Welch93]. Binding of CheY to FliM increases the probability of flagellar rotation in the CW direction [Barak92]. CCW rotation of the motor induces the flagellar filaments to coalesce into a bundle which propels the cell forward in a fairly straight line (run). CW rotation disrupts the bundle and causes the cell to tumble. The cell typically travels in a three-dimensional walk consisting of runs interspersed with random chaotic tumbling. CheZ is a cytosolic phosphatase which prevents overaccumulation of CheY-P by accelerating the decay of its aspartyl-phosphate residue [Hess87].

CheY-P is thus maintained during steady-state conditions at a level that generates the random walk [Manson98]. When an attractant molecule binds to the receptor, a conformational change is induced [Yeh93] which propagates across the membrane and results in a suppression of CheA autophosphorylation. Levels of CheY-P decrease and the cells tumble less frequently, causing an increase in their run lengths as they enter areas of higher attractant concentrations. The adaptation response is necessary, though, for the cells to respond properly to continually increasing attractant concentration. Adaptive methylation is carried out by two enzymes: the methyltransferase CheR and the methylesterase CheB [Toews79]. CheR is a constitutive enzyme which, through the use of S-adenosylmethionine, methylates glutamate residues in the cytoplasmic domains of the MCPs. CheB is a target for phosphotransfer from CheA, and the activated CheB-P functions as a methyl esterase which removes methyl groups from the MCPs, reducing their kinase activity. Under steady-state conditions, the addition of methyl groups by CheR is balanced by the methyl group removal by CheB-P and an intermediate level of receptor methylation is maintained, resulting in run-tumble behavior of the cell. When an attractant binds to a receptor and inhibits CheA activity, the levels of CheB-P drop. The decrease is slower than that for CheY-P though, since CheB-P is not a phosphate donor to CheZ. The rising level of methyl esters eventually stimulate histidine kinase activity and therefore counteract the effect of attractant binding to the receptor. This resets the receptor signal to its basal level [Falke97].

The components of the chemotaxis sensory system are arranged at one of the cell poles in tight clusters containing thousands of copies of each protein [Sourjik00]. Binding of an attractant results in an increase in the probability that CheA is inactive (unphosphorylated) and methylation of CheA on four specific glutamate residues increases the probability that that it is active (phosphorylated) [Borkovich92]. Lower levels of methylation reduce the activity of CheA but increase the affinity of the receptor for its attractant ligand [Li00a].


Subunit of: chemotaxis signaling complex - dipeptide sensing

Synonyms: MCP-IV chemotaxis signaling complex

Subunit composition of chemotaxis signaling complex - dipeptide sensing = [(CheA)2][CheW]2[(Tap)2]3
         CheA(L) histidine kinase = (CheA)2
         methyl accepting chemotaxis protein - dipeptide sensing = (Tap)2 (extended summary available)

Summary:
Chemotaxis in Escherichia coli is accomplished with a modified two-component signal transduction complex which transmits controlling signals to the flagellar motor complex. E.coli has four methyl-accepting chemotaxis protein (MCP)-type receptor complexes which recognize the following ligands: Tsr, serine;Tar, aspartate and maltose;Trg, ribose, galactose and glucose and Tap, dipeptides. Serine and aspartate bind directly to the receptor whereas maltose, ribose, galactose, glucose and dipeptides bind first to a periplasmic binding protein which then docks with its individual membrane receptor [Manson98].

The receptor complexes are ternary structures. The receptor-ligand interaction domain is located in the periplasm. Each receptor serves as the organizational framework for a receptor kinase signaling supermolecular complex formed in conjunction with histidine kinase CheA and other components of the signaling pathway [Falke97]. There are two transmembrane (TM) linker domains (CheW) which couple the methylation-dependent receptor to CheA. The receptors form homodimers with or without ligands [Gegner92]. CheA is a histidine kinase capable of autophosphorylation using ATP as a phosphodonor.The receptor complex dimers form trigonal units which in turn form a two-dimensional hexagonal lattice [Shimizu00] located usually at one pole of the cell. The Tsr and Tar receptors are the most abundant and the Tap, Trg receptors are less prevalent [Bren00].

CheA and CheY comprise a two-component signal transduction system where the signal is transmitted via phosphorylation from CheA to CheY (the response regulator). In several ways CheA/CheY differs from the standard two-component paradigm. Most significantly, CheY does not possess a DNA-binding domain and it doesn't act as a transcription factor. In the absence of activator ligand, CheA autophosphorylation is stimulated thus increasing the phosphotransfer from CheA to CheY, the messenger protein. CheY-P has a lower affinity for CheA than CheY, resulting in the dissociation of CheY-P from CheA. CheY-P has a higher affinity than CheY for the flagellar motor protein, FliM, a component of the motor supramolecular complex [Welch93]. Binding of CheY to FliM increases the probability of flagellar rotation in the CW direction [Barak92]. CCW rotation of the motor induces the flagellar filaments to coalesce into a bundle which propels the cell forward in a fairly straight line (run). CW rotation disrupts the bundle and causes the cell to tumble. The cell typically travels in a three-dimensional walk consisting of runs interspersed with random chaotic tumbling. CheZ is a cytosolic phosphatase which prevents overaccumulation of CheY-P by accelerating the decay of its aspartyl-phosphate residue [Hess87]. CheY-P is thus maintained during steady-state conditions at a level that generates the random walk [Manson98].

When an attractant molecule binds to the receptor, a conformational change is induced [Yeh93] which propagates across the membrane and results in a suppression of CheA autophosphorylation. Levels of CheY-P decrease and the cells tumble less frequently, causing an increase in their run lengths as they enter areas of higher attractant concentrations. The adaptation response is necessary, though, for the cells to respond properly to continually increasing attractant concentration. Adaptive methylation is carried out by two enzymes: the methyltransferase CheR and the methylesterase CheB [Toews79]. CheR is a constitutive enzyme which, through the use of S-adenosylmethionine, methylates glutamate residues in the cytoplasmic domains of the MCPs. CheB is a target for phosphotransfer from CheA, and the activated CheB-P functions as a methyl esterase which removes methyl groups from the MCPs, reducing their kinase activity. Under steady-state conditions, the addition of methyl groups by CheR is balanced by the methyl group removal by CheB-P and an intermediate level of receptor methylation is maintained, resulting in run-tumble behavior of the cell. When an attractant binds to a receptor and inhibits CheA activity, the levels of CheB-P drop. The decrease is slower than that for CheY-P though, since CheB-P is not a phosphate donor to CheZ. The rising level of methyl esters eventually stimulate histidine kinase activity and therefore counteract the effect of attractant binding to the receptor. This resets the receptor signal to its basal level [Falke97].

The components of the chemotaxis sensory system are arranged at one of the cell poles in tight clusters containing thousands of copies of each protein [Sourjik00]. Binding of an attractant results in an increase in the probability that CheA is inactive (unphosphorylated) and methylation of CheA on four specific glutamate residues increases the probability that that it is active (phosphorylated) [Borkovich92]. Lower levels of methylation reduce the activity of CheA but increase the affinity of the receptor for its attractant ligand [Li00a].


Subunit of: chemotaxis signaling complex - serine sensing

Synonyms: MCP-I signaling complex

Subunit composition of chemotaxis signaling complex - serine sensing = [CheW]2[(CheA)2][(Tsr)2]3
         CheA(L) histidine kinase = (CheA)2
         methyl accepting chemotaxis protein - serine sensing = (Tsr)2 (extended summary available)

Summary:
Chemotaxis in Escherichia coli is accomplished with a modified two-component signal transduction complex which transmits controlling signals to the flagellar motor complex. E. coli has four methyl-accepting chemotaxis protein (MCP)-type receptor complexes which recognize the following ligands: Tsr, serine;Tar, aspartate and maltose;Trg, ribose, galactose and glucose and Tap, dipeptides. Serine and aspartate bind directly to the receptor whereas maltose, ribose, galactose, glucose and dipeptides bind first to a periplasmic binding protein which then docks with its individual membrane receptor [Manson98].

The receptor complexes are ternary structures. The receptor-ligand interaction domain is located in the periplasm. Each receptor serves as the organizational framework for a receptor kinase signaling supramolecular complex formed in conjunction with histidine kinase CheA and other components of the signaling pathway [Falke97]. There are two transmembrane (TM) linker domains (CheW) which couple the methylation-dependent receptor to CheA. The receptors form homodimers with or without ligands [Gegner92]. CheA is a histidine kinase capable of autophosphorylation using ATP as a phosphodonor. The receptor complex dimers form trigonal units which in turn form a two-dimensional hexagonal lattice [Shimizu00] located usually at one pole of the cell. Modeling of the Tsr chemoreceptor array suggests that the core signaling complex consists of a CheA/CheW dimer which bridges adjacent receptor trimers [Liu12a]. The Tsr and Tar receptors are the most abundant and the Tap, Trg receptors are less prevalent [Bren00].

CheA and CheY comprise a two-component signal transduction system where the signal is transmitted via phosphorylation from CheA to CheY (the response regulator). In several ways CheA/CheY differs from the standard two-component paradigm. Most significantly, CheY does not possess a DNA-binding domain and it doesn't act as a transcription factor. In the absence of activator ligand, CheA autophosphorylation is stimulated thus increasing the phosphotransfer from CheA to CheY, the messenger protein. CheY-P has a lower affinity for CheA than CheY, resulting in the dissociation of CheY-P from CheA. CheY-P has a higher affinity than CheY for the flagellar motor protein, FliM, a component of the motor supramolecular complex [Welch93]. Binding of CheY to FliM increases the probability of flagellar rotation in the CW direction [Barak92]. CCW rotation of the motor induces the flagellar filaments to coalesce into a bundle which propels the cell forward in a fairly straight line (run). CW rotation disrupts the bundle and causes the cell to tumble. The cell typically travels in a three-dimensional walk consisting of runs interspersed with random chaotic tumbling. CheZ is a cytosolic phosphatase which prevents overaccumulation of CheY-P by accelerating the decay of its aspartyl-phosphate residue [Hess87]. CheY-P is thus maintained during steady-state conditions at a level that generates the random walk [Manson98].

When an attractant molecule binds to the receptor, a conformational change is induced [Yeh93] which propagates across the membrane and results in a suppression of CheA autophosphorylation. Levels of CheY-P decrease and the cells tumble less frequently, causing an increase in their run lengths as they enter areas of higher attractant concentrations. The adaptation response is necessary, though, for the cells to respond properly to continually increasing attractant concentration. Adaptive methylation is carried out by two enzymes: the methyltransferase CheR and the methylesterase CheB [Toews79]. CheR is a constitutive enzyme which, through the use of S-adenosylmethionine, methylates glutamate residues in the cytoplasmic domains of the MCPs. CheB is a target for phosphotransfer from CheA, and the activated CheB-P functions as a methyl esterase which removes methyl groups from the MCPs, reducing their kinase activity. Under steady-state conditions, the addition of methyl groups by CheR is balanced by the methyl group removal by CheB-P and an intermediate level of receptor methylation is maintained, resulting in run-tumble behavior of the cell. When an attractant binds to a receptor and inhibits CheA activity, the levels of CheB-P drop. The decrease is slower than that for CheY-P though, since CheB-P is not a phosphate donor to CheZ. The rising level of methyl esters eventually stimulate histidine kinase activity and therefore counteract the effect of attractant binding to the receptor. This resets the receptor signal to its basal level [Falke97].

The components of the chemotaxis sensory system are arranged at one of the cell poles in tight clusters containing thousands of copies of each protein [Sourjik00]. Binding of an attractant results in an increase in the probability that CheA is inactive (unphosphorylated) and methylation of CheA on four specific glutamate residues increases the probability that that it is active (phosphorylated) [Borkovich92]. Lower levels of methylation reduce the activity of CheA but increase the affinity of the receptor for its attractant ligand [Li00a].

Citations: [Hall12]


Subunit of: chemotaxis signaling complex - aspartate sensing

Synonyms: MCP-II signaling complex

Subunit composition of chemotaxis signaling complex - aspartate sensing = [(CheA)2][CheW]2[(Tar)2]3
         CheA(L) histidine kinase = (CheA)2
         methyl accepting chemotaxis protein Tar = (Tar)2 (extended summary available)

Summary:
The tar gene product is one of four methyl-accepting chemotaxis proteins (MCPs) in E. coli. MCP-II is the receptor for the attractant L-aspartate and related amino acids and dicarboxylic acids. MCP-II also interacts with the periplasmic maltose-binding protein to mediate taxis to the attractant maltose. It also responds to the repellents cobalt and nickel and is thermosensitive. [Nara96, Gardina97, Gardina92, Krikos83, Wang80, Chi97, Hoch95, Neidhardt96, Salman07, Jiang09a].

Chemotaxis in Escherichia coli is accomplished with a modified two-component signal transduction complex which transmits controlling signals to the flagellar motor complex. E.coli has four methyl-accepting chemotaxis protein (MCP)-type receptor complexes which recognize the following ligands: Tsr, serine;Tar, aspartate and maltose;Trg, ribose, galactose and glucose and Tap, dipeptides. Serine and aspartate bind directly to the receptor whereas maltose, ribose, galactose, glucose and dipeptides bind first to a periplasmic binding protein which then docks with its individual membrane receptor [Manson98].

The receptor complexes are ternary structures. The receptor-ligand interaction domain is located in the periplasm. Each receptor serves as the organizational framework for a receptor kinase signaling supermolecular complex formed in conjunction with histidine kinase CheA and other components of the signaling pathway [Falke97]. There are two transmembrane (TM) linker domains (CheW) which couple the methylation-dependent receptor to CheA. The receptors form homodimers with or without ligands [Gegner92]. CheA is a histidine kinase capable of autophosphorylation using ATP as a phosphodonor. The receptor complex dimers form trigonal units which in turn form a two-dimensional hexagonal lattice [Shimizu00] located usually at one pole of the cell. The Tsr and Tar receptors are the most abundant and the Tap, Trg receptors are less prevalent [Bren00].

CheA and CheY comprise a two-component signal transduction system where the signal is transmitted via phosphorylation from CheA to CheY (the response regulator). In several ways CheA/CheY differs from the standard two-component paradigm. Most significantly, CheY does not possess a DNA-binding domain and it doesn't act as a transcription factor. In the absence of activator ligand, CheA autophosphorylation is stimulated thus increasing the phosphotransfer from CheA to CheY, the messenger protein. CheY-P has a lower affinity for CheA than CheY, resulting in the dissociation of CheY-P from CheA. CheY-P has a higher affinity than CheY for the flagellar motor protein, FliM, a component of the motor supramolecular complex [Welch93]. Binding of CheY to FliM increases the probability of flagellar rotation in the CW direction [Barak92]. CCW rotation of the motor induces the flagellar filaments to coalesce into a bundle which propels the cell forward in a fairly straight line (run). CW rotation disrupts the bundle and causes the cell to tumble. The cell typically travels in a three-dimensional walk consisting of runs interspersed with random chaotic tumbling. CheZ is a cytosolic phosphatase which prevents overaccumulation of CheY-P by accelerating the decay of its aspartyl-phosphate residue [Hess87]. CheY-P is thus maintained during steady-state conditions at a level that generates the random walk [Manson98].

When an attractant molecule binds to the receptor, a conformational change is induced [Yeh93] which propagates across the membrane and results in a suppression of CheA autophosphorylation. Levels of CheY-P decrease and the cells tumble less frequently, causing an increase in their run lengths as they enter areas of higher attractant concentrations. The adaptation response is necessary, though, for the cells to respond properly to continually increasing attractant concentration. Adaptive methylation is carried out by two enzymes: the methyltransferase CheR and the methylesterase CheB [Toews79]. CheR is a constitutive enzyme which, through the use of S-adenosylmethionine, methylates glutamate residues in the cytoplasmic domains of the MCPs. CheB is a target for phosphotransfer from CheA, and the activated CheB-P functions as a methyl esterase which removes methyl groups from the MCPs, reducing their kinase activity. Under steady-state conditions, the addition of methyl groups by CheR is balanced by the methyl group removal by CheB-P and an intermediate level of receptor methylation is maintained, resulting in run-tumble behavior of the cell. When an attractant binds to a receptor and inhibits CheA activity, the levels of CheB-P drop. The decrease is slower than that for CheY-P though, since CheB-P is not a phosphate donor to CheZ. The rising level of methyl esters eventually stimulate histidine kinase activity and therefore counteract the effect of attractant binding to the receptor. This resets the receptor signal to its basal level [Falke97].

The components of the chemotaxis sensory system are arranged at one of the cell poles in tight clusters containing thousands of copies of each protein [Sourjik00]. Binding of an attractant results in an increase in the probability that CheA is inactive (unphosphorylated) and methylation of CheA on four specific glutamate residues increases the probability that that it is active (phosphorylated) [Borkovich92]. Lower levels of methylation reduce the activity of CheA but increase the affinity of the receptor for its attractant ligand [Li00a].


Sequence Features

Feature Class Location Citations Comment State
Intrinsic-Sequence-Variant 1 -> 97
[UniProt10a]
Alternate sequence: MSMDISDFYQTFFDEADELLADMEQHLLVLQPEAPDAEQLNAIFRAAHSIKGGAGTFGFSVLQETTHLMENLLDEARRGEMQLNTDIINLFLETKDI → missing; UniProt: (in isoform cheA(S));
 
Conserved-Region 1 -> 105
[UniProt09]
UniProt: HPt;
 
Phosphorylation-Modification 48
[UniProt08]
UniProt: Phosphohistidine; by autocatalysis;
Unmodified
Amino-Acid-Site 98
Alternative translation initiation codon.
 
Sequence-Conflict 166
[Kofoid91, UniProt10a]
Alternate sequence: R → P; UniProt: (in Ref. 1; AAA23573/AAA23574);
 
Conserved-Region 257 -> 509
[UniProt09]
UniProt: Histidine kinase;
 
Conserved-Region 511 -> 646
[UniProt09]
UniProt: CheW-like;
 
Sequence-Conflict 548 -> 565
[Mutoh86, UniProt10a]
Alternate sequence: GERVLEVRGEYLPIVELW → ASGCWKCGVNICPSSNCG; UniProt: (in Ref. 5; AAA23564);
 
Sequence-Conflict 606
[Mutoh86, UniProt10a]
Alternate sequence: V → A; UniProt: (in Ref. 5; AAA23564);
 


Gene Local Context (not to scale): ?

Transcription Unit:

Notes:

Exons/Introns:

History:
10/20/97 Gene b1888 from Blattner lab Genbank (v. M52) entry merged into EcoCyc gene EG10146; confirmed by SwissProt match.


References

Baba06: Baba T, Ara T, Hasegawa M, Takai Y, Okumura Y, Baba M, Datsenko KA, Tomita M, Wanner BL, Mori H (2006). "Construction of Escherichia coli K-12 in-frame, single-gene knockout mutants: the Keio collection." Mol Syst Biol 2;2006.0008. PMID: 16738554

Barak04: Barak R, Eisenbach M (2004). "Co-regulation of acetylation and phosphorylation of CheY, a response regulator in chemotaxis of Escherichia coli." J Mol Biol 342(2);375-81. PMID: 15327941

Barak92: Barak R, Eisenbach M (1992). "Correlation between phosphorylation of the chemotaxis protein CheY and its activity at the flagellar motor." Biochemistry 31(6);1821-6. PMID: 1737035

Bhatnagar12: Bhatnagar J, Sircar R, Borbat PP, Freed JH, Crane BR (2012). "Self-association of the histidine kinase CheA as studied by pulsed dipolar ESR spectroscopy." Biophys J 102(9);2192-201. PMID: 22824284

Borkovich89: Borkovich KA, Kaplan N, Hess JF, Simon MI (1989). "Transmembrane signal transduction in bacterial chemotaxis involves ligand-dependent activation of phosphate group transfer." Proc Natl Acad Sci U S A 86(4);1208-12. PMID: 2645576

Borkovich90: Borkovich KA, Simon MI (1990). "The dynamics of protein phosphorylation in bacterial chemotaxis." Cell 63(6);1339-48. PMID: 2261645

Borkovich92: Borkovich KA, Alex LA, Simon MI (1992). "Attenuation of sensory receptor signaling by covalent modification." Proc Natl Acad Sci U S A 89(15);6756-60. PMID: 1495964

Bourret93: Bourret RB, Davagnino J, Simon MI (1993). "The carboxy-terminal portion of the CheA kinase mediates regulation of autophosphorylation by transducer and CheW." J Bacteriol 175(7);2097-101. PMID: 8384620

Bren00: Bren A, Eisenbach M (2000). "How signals are heard during bacterial chemotaxis: protein-protein interactions in sensory signal propagation." J Bacteriol 182(24);6865-73. PMID: 11092844

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Other References Related to Gene Regulation

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Yu06b: Yu HH, Di Russo EG, Rounds MA, Tan M (2006). "Mutational analysis of the promoter recognized by Chlamydia and Escherichia coli sigma(28) RNA polymerase." J Bacteriol 188(15);5524-31. PMID: 16855242

Yu06c: Yu HH, Kibler D, Tan M (2006). "In Silico Prediction and Functional Validation of {sigma}28-Regulated Genes in Chlamydia and Escherichia coli." J Bacteriol 188(23);8206-8212. PMID: 16997971

Zahrl06: Zahrl D, Wagner M, Bischof K, Koraimann G (2006). "Expression and assembly of a functional type IV secretion system elicit extracytoplasmic and cytoplasmic stress responses in Escherichia coli." J Bacteriol 188(18);6611-21. PMID: 16952953


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Please cite the following article in publications resulting from the use of EcoCyc: Nucleic Acids Research 41:D605-12 2013
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