|Gene:||tar||Accession Numbers: EG10988 (EcoCyc), b1886, ECK1887|
Synonyms: cheM, MCP-II, aspartate chemoreceptor protein, Tar dimer, chemotaxis signaling protein II
Component of: chemotaxis signaling complex - aspartate sensing (extended summary available)
Subunit composition of methyl accepting chemotaxis protein Tar = [Tar]2
The tar gene product is one of four methyl-accepting chemotaxis proteins (MCPs) in E. coli K-12. MCP-II is the receptor for the attractants aspartate and maltose and the repellents nickel and cobalt [Reader79, Wang80, Springer77]. Tar is the primary receptor for the amino acids aspartate, asparagine and glutamate; in strains lacking the Tsr receptor, Tar can mediate a chemotactic response to serine, cysteine, glycine, alanine and asparagine [Yang15]. Tar is responsible for mediating an attractant response to phenol [Imae87] and Tsr and Tar mediate a chemotactic response to changes in pH [Krikos85].
E. coli Tar is a homodimeric inner membrane protein; the Tar monomer consists of a periplasmic, ligand-sensing domain, two trans-membrane segments (TM1 and TM2) and a cytoplasmic signaling domain which is predominantly alpha-helical in structure and is predicted to contain 4 methylation sites [Lynch91, Bowie95, Le96]. The cytoplasmic domain of Tar is subject to methylation and demethylation at the carboxyl groups of glutamic acid residues [DeFranco80, Engstrom80, Krikos83]. Methylation and demethylation of MCPs in E. coli K-12 is catalysed by the CheR methyltransferase and the CheB methylesterase.
Aspartate binds directly to the Tar receptor whereas maltose detection is mediated via the periplasmic maltose binding protein [Manson85, Wolff88, Mowbray87, Gardina92, Gardina97, Gardina98, Zhang99]. Aspartate binding to a purified Tar receptor generates a downward piston motion of TM1 relative to TM2 [Ottemann99]
The cytoplasmic domains of the four E. coli MCPs have a high degree of sequence similarity [Krikos83, Le96, Alexander07]. Tar contains a HAMP domain (present in histidine kinases, adenylate cyclases, methyl accepting chemotaxis proteins, phosphatases) which is located between the transmembrane region of the molecule and the cytoplasmic signalling region. Tsr HAMP domains have been shown to mediate input/ouptut signaling [Ames08, Zhou09, Zhou11, Ames13, Samanta15] (and reviewed in [Parkinson10]).
E. coli MCPs form ternary complexes with the cytoplasmic proteins CheA and CheW [Gegner92]. Tar and Tsr are considered to be high-abundance receptors while Tap and Trg are low-abundance [Hazelbauer81, Hazelbauer81a, Harayama82].
Novel chemoeffectors specific for Tar have been identified as have two antagonistic compounds which bind to Tar but do not induce a chemotactic response [Bi13a].
tar: taxis to aspartate and from repellents
Locations: inner membrane
|Map Position: [1,969,054 <- 1,970,715] (42.44 centisomes, 153°)||Length: 1662 bp / 553 aa|
Molecular Weight of Polypeptide: 59.944 kD (from nucleotide sequence), 60.0 kD (experimental) [Wang80 ]
Unification Links: ASAP:ABE-0006290 , CGSC:122 , DIP:DIP-10956N , DisProt:DP00294 , EchoBASE:EB0981 , EcoGene:EG10988 , EcoliWiki:b1886 , ModBase:P07017 , OU-Microarray:b1886 , PortEco:tar , PR:PRO_000024026 , Pride:P07017 , Protein Model Portal:P07017 , RefSeq:NP_416400 , RegulonDB:EG10988 , SMR:P07017 , String:511145.b1886 , Swiss-Model:P07017 , UniProt:P07017
Relationship Links: InterPro:IN-FAMILY:IPR003122 , InterPro:IN-FAMILY:IPR003660 , InterPro:IN-FAMILY:IPR004089 , InterPro:IN-FAMILY:IPR004090 , InterPro:IN-FAMILY:IPR004091 , PDB:Structure:2ASR , PDB:Structure:2L9G , Pfam:IN-FAMILY:PF00015 , Pfam:IN-FAMILY:PF00672 , Pfam:IN-FAMILY:PF02203 , Prints:IN-FAMILY:PR00260 , Prosite:IN-FAMILY:PS00538 , Prosite:IN-FAMILY:PS50111 , Prosite:IN-FAMILY:PS50885 , Smart:IN-FAMILY:SM00283 , Smart:IN-FAMILY:SM00304 , Smart:IN-FAMILY:SM00319
|Biological Process:||GO:0006935 - chemotaxis
[UniProtGOA11a, GOA01a, Silverman77]
GO:0007165 - signal transduction [UniProtGOA11a, GOA01a]
|Molecular Function:||GO:0004871 - signal transducer activity
[UniProtGOA11a, GOA01a, Springer77]
GO:0004888 - transmembrane signaling receptor activity [GOA01a, Springer77]
GO:0005515 - protein binding [Arifuzzaman06, Rajagopala09]
GO:0043424 - protein histidine kinase binding [Gegner92]
|Cellular Component:||GO:0005887 - integral component of plasma membrane
[Ridgway77, Krikos83, Lynch91]
GO:0005886 - plasma membrane [UniProtGOA11, UniProtGOA11a]
GO:0016020 - membrane [UniProtGOA11a, GOA01a]
GO:0016021 - integral component of membrane [UniProtGOA11a, GOA01a]
|MultiFun Terms:||cell processes → motility, chemotaxis, energytaxis (aerotaxis, redoxtaxis etc)|
|cell structure → membrane|
|regulation → type of regulation → posttranscriptional → inhibition / activation of enzymes|
|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]|
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)
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, Jiang09, Wheatley15].
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 (reviewed in [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 (reviewed in [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 [Li00].
|Transmembrane-Region||7 -> 33|
|Protein-Segment||64 -> 73|
|Transmembrane-Region||191 -> 211|
|Conserved-Region||214 -> 266|
|Conserved-Region||271 -> 500|
10/20/97 Gene b1886 from Blattner lab Genbank (v. M52) entry merged into EcoCyc gene EG10988; confirmed by SwissProt match.
Alexander07: Alexander RP, Zhulin IB (2007). "Evolutionary genomics reveals conserved structural determinants of signaling and adaptation in microbial chemoreceptors." Proc Natl Acad Sci U S A 104(8);2885-90. PMID: 17299051
Ames13: Ames P, Zhou Q, Parkinson JS (2013). "HAMP domain structural determinants for signalling and sensory adaptation in Tsr, the Escherichia coli serine chemoreceptor." Mol Microbiol. PMID: 24205875
Arifuzzaman06: Arifuzzaman M, Maeda M, Itoh A, Nishikata K, Takita C, Saito R, Ara T, Nakahigashi K, Huang HC, Hirai A, Tsuzuki K, Nakamura S, Altaf-Ul-Amin M, Oshima T, Baba T, Yamamoto N, Kawamura T, Ioka-Nakamichi T, Kitagawa M, Tomita M, Kanaya S, Wada C, Mori H (2006). "Large-scale identification of protein-protein interaction of Escherichia coli K-12." Genome Res 16(5);686-91. PMID: 16606699
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
Bi13a: Bi S, Yu D, Si G, Luo C, Li T, Ouyang Q, Jakovljevic V, Sourjik V, Tu Y, Lai L (2013). "Discovery of novel chemoeffectors and rational design of Escherichia coli chemoreceptor specificity." Proc Natl Acad Sci U S A 110(42);16814-9. PMID: 24082101
Boyd80: Boyd A, Simon MI (1980). "Multiple electrophoretic forms of methyl-accepting chemotaxis proteins generated by stimulus-elicited methylation in Escherichia coli." J Bacteriol 143(2);809-15. PMID: 6782079
Chelsky80: Chelsky D, Dahlquist FW (1980). "Structural studies of methyl-accepting chemotaxis proteins of Escherichia coli: evidence for multiple methylation sites." Proc Natl Acad Sci U S A 77(5);2434-8. PMID: 6994098
Chi97: Chi YI, Yokota H, Kim SH (1997). "Apo structure of the ligand-binding domain of aspartate receptor from Escherichia coli and its comparison with ligand-bound or pseudoligand-bound structures." FEBS Lett 1997;414(2);327-32. PMID: 9315712
Draheim05: Draheim RR, Bormans AF, Lai RZ, Manson MD (2005). "Tryptophan residues flanking the second transmembrane helix (TM2) set the signaling state of the Tar chemoreceptor." Biochemistry 44(4);1268-77. PMID: 15667220
Falke97: Falke JJ, Bass RB, Butler SL, Chervitz SA, Danielson MA (1997). "The two-component signaling pathway of bacterial chemotaxis: a molecular view of signal transduction by receptors, kinases, and adaptation enzymes." Annu Rev Cell Dev Biol 13;457-512. PMID: 9442881
Gardina92: Gardina P, Conway C, Kossman M, Manson M (1992). "Aspartate and maltose-binding protein interact with adjacent sites in the Tar chemotactic signal transducer of Escherichia coli." J Bacteriol 1992;174(5);1528-36. PMID: 1537797
Gardina97: Gardina PJ, Bormans AF, Hawkins MA, Meeker JW, Manson MD (1997). "Maltose-binding protein interacts simultaneously and asymmetrically with both subunits of the Tar chemoreceptor." Mol Microbiol 1997;23(6);1181-91. PMID: 9106209
Gardina98: Gardina PJ, Bormans AF, Manson MD (1998). "A mechanism for simultaneous sensing of aspartate and maltose by the Tar chemoreceptor of Escherichia coli." Mol Microbiol 29(5);1147-54. PMID: 9767583
Gegner92: Gegner JA, Graham DR, Roth AF, Dahlquist FW (1992). "Assembly of an MCP receptor, CheW, and kinase CheA complex in the bacterial chemotaxis signal transduction pathway." Cell 70(6);975-82. PMID: 1326408
Gerdes03: Gerdes SY, Scholle MD, Campbell JW, Balazsi G, Ravasz E, Daugherty MD, Somera AL, Kyrpides NC, Anderson I, Gelfand MS, Bhattacharya A, Kapatral V, D'Souza M, Baev MV, Grechkin Y, Mseeh F, Fonstein MY, Overbeek R, Barabasi AL, Oltvai ZN, Osterman AL (2003). "Experimental determination and system level analysis of essential genes in Escherichia coli MG1655." J Bacteriol 185(19);5673-84. PMID: 13129938
Hazelbauer81a: Hazelbauer GL, Engstrom P (1981). "Multiple forms of methyl-accepting chemotaxis proteins distinguished by a factor in addition to multiple methylation." J Bacteriol 145(1);35-42. PMID: 7007319
Joyce06: Joyce AR, Reed JL, White A, Edwards R, Osterman A, Baba T, Mori H, Lesely SA, Palsson BO, Agarwalla S (2006). "Experimental and computational assessment of conditionally essential genes in Escherichia coli." J Bacteriol 188(23);8259-71. PMID: 17012394
Kundu97: Kundu TK, Kusano S, Ishihama A (1997). "Promoter selectivity of Escherichia coli RNA polymerase sigmaF holoenzyme involved in transcription of flagellar and chemotaxis genes." J Bacteriol 179(13);4264-9. PMID: 9209042
Lai08: Lai RZ, Bormans AF, Draheim RR, Wright GA, Manson MD (2008). "The region preceding the C-terminal NWETF pentapeptide modulates baseline activity and aspartate inhibition of Escherichia coli Tar." Biochemistry 47(50);13287-95. PMID: 19053273
Lynch91: Lynch BA, Koshland DE (1991). "Disulfide cross-linking studies of the transmembrane regions of the aspartate sensory receptor of Escherichia coli." Proc Natl Acad Sci U S A 88(23);10402-6. PMID: 1660136
Mise14: Mise T, Matsunami H, Samatey FA, Maruyama IN (2014). "Crystallization and preliminary X-ray diffraction analysis of the periplasmic domain of the Escherichia coli aspartate receptor Tar and its complex with aspartate." Acta Crystallogr F Struct Biol Commun 70(Pt 9);1219-23. PMID: 25195895
Nara96: Nara T, Kawagishi I, Nishiyama S, Homma M, Imae Y (1996). "Modulation of the thermosensing profile of the Escherichia coli aspartate receptor tar by covalent modification of its methyl-accepting sites." J Biol Chem 1996;271(30);17932-6. PMID: 8663384
Neidhardt96: Neidhardt FC, Curtiss III R, Ingraham JL, Lin ECC, Low Jr KB, Magasanik B, Reznikoff WS, Riley M, Schaechter M, Umbarger HE "Escherichia coli and Salmonella, Cellular and Molecular Biology, Second Edition." American Society for Microbiology, Washington, D.C., 1996.
Nishiyama99: Nishiyama S, Maruyama IN, Homma M, Kawagishi I (1999). "Inversion of thermosensing property of the bacterial receptor Tar by mutations in the second transmembrane region." J Mol Biol 286(5);1275-84. PMID: 10064695
Pakula92: Pakula AA, Simon MI (1992). "Determination of transmembrane protein structure by disulfide cross-linking: the Escherichia coli Tar receptor." Proc Natl Acad Sci U S A 89(9);4144-8. PMID: 1315053
Samanta15: Samanta D, Borbat PP, Dzikovski B, Freed JH, Crane BR (2015). "Bacterial chemoreceptor dynamics correlate with activity state and are coupled over long distances." Proc Natl Acad Sci U S A 112(8);2455-60. PMID: 25675479
Shimizu00: Shimizu TS, Le Novere N, Levin MD, Beavil AJ, Sutton BJ, Bray D (2000). "Molecular model of a lattice of signalling proteins involved in bacterial chemotaxis." Nat Cell Biol 2(11);792-6. PMID: 11056533
Springer77: Springer MS, Goy MF, Adler J (1977). "Sensory transduction in Escherichia coli: two complementary pathways of information processing that involve methylated proteins." Proc Natl Acad Sci U S A 74(8);3312-6. PMID: 333433
Tatsuno96: Tatsuno I, Homma M, Oosawa K, Kawagishi I (1996). "Signaling by the Escherichia coli aspartate chemoreceptor Tar with a single cytoplasmic domain per dimer." Science 274(5286);423-5. PMID: 8832891
Toews79: Toews ML, Goy MF, Springer MS, Adler J (1979). "Attractants and repellents control demethylation of methylated chemotaxis proteins in Escherichia coli." Proc Natl Acad Sci U S A 76(11);5544-8. PMID: 392505
Welch93: Welch M, Oosawa K, Aizawa S, Eisenbach M (1993). "Phosphorylation-dependent binding of a signal molecule to the flagellar switch of bacteria." Proc Natl Acad Sci U S A 90(19);8787-91. PMID: 8415608
Wheatley15: Wheatley RW, Juers DH, Lev BB, Huber RE, Noskov SY (2015). "Elucidating factors important for monovalent cation selectivity in enzymes: E. coli β-galactosidase as a model." Phys Chem Chem Phys 17(16);10899-909. PMID: 25820412
Wright11: Wright GA, Crowder RL, Draheim RR, Manson MD (2011). "Mutational analysis of the transmembrane helix 2-HAMP domain connection in the Escherichia coli aspartate chemoreceptor tar." J Bacteriol 193(1);82-90. PMID: 20870768
Yeh93: Yeh JI, Biemann HP, Pandit J, Koshland DE, Kim SH (1993). "The three-dimensional structure of the ligand-binding domain of a wild-type bacterial chemotaxis receptor. Structural comparison to the cross-linked mutant forms and conformational changes upon ligand binding." J Biol Chem 268(13);9787-92. PMID: 8486661
Zhang99: Zhang Y, Gardina PJ, Kuebler AS, Kang HS, Christopher JA, Manson MD (1999). "Model of maltose-binding protein/chemoreceptor complex supports intrasubunit signaling mechanism." Proc Natl Acad Sci U S A 96(3);939-44. PMID: 9927672
Zhou09: Zhou Q, Ames P, Parkinson JS (2009). "Mutational analyses of HAMP helices suggest a dynamic bundle model of input-output signalling in chemoreceptors." Mol Microbiol 73(5);801-14. PMID: 19656294
Constantinidou06: Constantinidou C, Hobman JL, Griffiths L, Patel MD, Penn CW, Cole JA, Overton TW (2006). "A reassessment of the FNR regulon and transcriptomic analysis of the effects of nitrate, nitrite, NarXL, and NarQP as Escherichia coli K12 adapts from aerobic to anaerobic growth." J Biol Chem 281(8);4802-15. PMID: 16377617
Helmann87: Helmann JD, Chamberlin MJ (1987). "DNA sequence analysis suggests that expression of flagellar and chemotaxis genes in Escherichia coli and Salmonella typhimurium is controlled by an alternative sigma factor." Proc Natl Acad Sci U S A 84(18);6422-4. PMID: 3306678
Liu95a: Liu X, Matsumura P (1995). "An alternative sigma factor controls transcription of flagellar class-III operons in Escherichia coli: gene sequence, overproduction, purification and characterization." Gene 164(1);81-4. PMID: 7590326
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