|Gene:||ftsZ||Accession Numbers: EG10347 (EcoCyc), b0095, ECK0096|
Synonyms: sfiB, sulB
Assembly of FtsZ into a ring structure (the Z ring, [Bi91]) at the future cell division site is the earliest known event in cell division. FtsZ is the most highly conserved of the proteins that eventually comprise the septal ring structure; homologs of FtsZ are nearly universally present in bacteria as well as in many archaea, some chloroplasts and a few mitochondria [Vaughan04].
FtsZ is essential [Dai91]; it binds GTP and has Mg2+-dependent GTPase activity [RayChaudhuri92, deBoer92]. Assembly of FtsZ into protein filaments is dynamic and regulated by GTP hydrolysis [Mukherjee94], resembling tubulin [Mukherjee98]. Turnover of FtsZ within the Z ring is extremely rapid, with the rate-limiting step for turnover likely to be GTP hydrolysis [Anderson04, Romberg04].
The position of the FtsZ ring structure marks the cell division site and is serving as the assembly point to which other proteins of the cell division machinery are recruited. Based on studies of mutants, FtsA and ZipA initially associate with FtsZ, followed by addition of FtsEX, FtsK, FtsQ, FtsL/FtsB, FtsW, FtsI, FtsN and AmiC, apparently in this defined order.
The question of how FtsZ itself is positioned precisely at mid-cell, enabling a normal cell division event, has not been definitively answered yet. Both nucleoid occlusion and the Min system appear to play a role in division site selection; the hypothesis has been discussed in detail [Norris04]. Nucleoid occlusion describes a process by which the presence of the nucleoid inhibits Z ring formation at that site. When the nucleoid structure is perturbed by a block in transcription, nucleoid occlusion is affected; thus, the process may depend on the specific organization of the nucleoid [Sun04]. Both SulA and MinC are negative regulators of Z ring assembly [Bi93]. SulA interacts directly with FtsZ [Higashitani95, Cordell03] and inhibits GTPase activity and polymerization in vitro [Mukherjee98a, Trusca98] and FtsZ ring formation in vivo [Justice00]. MinC also interacts with FtsZ directly and prevents FtsZ polymerization without inhibiting its GTPase activity [Hu99a, Pichoff01]. The MinCD proteins oscillate between the two cell poles; this behavior may allow Z ring formation at mid-cell because the time-integrated concentration of MinCD is lowest at mid-cell. A conflicting report asserts that MinCD does not block Z ring formation, but instead blocks FtsA association with the Z ring [Justice00].
In studies using GFP-labeled FtsZ, FtsZ outside of the Z ring was found to move rapidly in a helix-like pattern along the cell, similar to the movements of the Min proteins. The presence of a dynamic, helical cytoskeleton was proposed [Thanedar04]. Supporting this hypothesis, FtsZ was found to be involved in maintaining cell shape [Varma04].
The domain structure of FtsZ has been described [Vaughan04]. A highly conserved central domain is structurally and functionally homologous to tubulin; it contains the dimerization domain [Di99]. The C-terminal core domain consists of 12 amino acids essential for FtsA and ZipA binding [Ma99].
The crystal structure of a C-terminal fragment of FtsZ in complex with ZipA has been solved [Mosyak00].
Compounds with activity against E. coli FtsZ, with potential utility as broad-spectrum antimicrobials, have been recently isolated and characterized [Margalit04].
Regulation of FtsZ expression and activity is complex and has been summarized in [Addinall02].
|Map Position: [105,305 -> 106,456] (2.27 centisomes)||Length: 1152 bp / 383 aa|
Molecular Weight of Polypeptide: 40.324 kD (from nucleotide sequence)
Unification Links: ASAP:ABE-0000333 , CGSC:143 , DIP:DIP-31873N , EchoBASE:EB0343 , EcoGene:EG10347 , EcoliWiki:b0095 , Mint:MINT-8092601 , ModBase:P0A9A6 , OU-Microarray:b0095 , PortEco:ftsZ , PR:PRO_000022726 , Pride:P0A9A6 , Protein Model Portal:P0A9A6 , RefSeq:NP_414637 , RegulonDB:EG10347 , SMR:P0A9A6 , String:511145.b0095 , Swiss-Model:P0A9A6 , UniProt:P0A9A6
Relationship Links: InterPro:IN-FAMILY:IPR000158 , InterPro:IN-FAMILY:IPR003008 , InterPro:IN-FAMILY:IPR008280 , InterPro:IN-FAMILY:IPR018316 , InterPro:IN-FAMILY:IPR020805 , InterPro:IN-FAMILY:IPR024757 , PDB:Structure:1F47 , Pfam:IN-FAMILY:PF00091 , Pfam:IN-FAMILY:PF12327 , Prints:IN-FAMILY:PR00423 , Prosite:IN-FAMILY:PS01134 , Prosite:IN-FAMILY:PS01135 , Smart:IN-FAMILY:SM00864 , Smart:IN-FAMILY:SM00865
|Biological Process:||GO:0051258 - protein polymerization
[GOA06, GOA01a, Cho11b, Ma96a]
GO:0051301 - cell division [UniProtGOA11a, Camberg11, Dai91]
GO:0000917 - barrier septum assembly [UniProtGOA11a]
GO:0006184 - GTP catabolic process [GOA01a]
GO:0007049 - cell cycle [UniProtGOA11a]
GO:0043093 - FtsZ-dependent cytokinesis [GOA06]
|Molecular Function:||GO:0003924 - GTPase activity
[GOA06, GOA01a, deBoer92, RayChaudhuri92]
GO:0005515 - protein binding [Fenton13, Butland05, Rajagopala14, Huang96, DurandHeredia12, Hale11, DurandHeredia11, Shen09, Ebersbach08, Shiomi08, Shiomi07, Karimova05, Masuda12, Alexeeva10, Liu99, Corbin07, Mosyak00]
GO:0005525 - GTP binding [UniProtGOA11a, GOA06, GOA01a, deBoer92, RayChaudhuri92]
GO:0042802 - identical protein binding [Salvarelli11, Masuda12, Hale11, DurandHeredia11, Shen09, Ebersbach08]
GO:0000166 - nucleotide binding [UniProtGOA11a]
|Cellular Component:||GO:0005737 - cytoplasm
[UniProtGOA11, UniProtGOA11a, GOA06, GOA01a, Pla91]
GO:0032153 - cell division site [GOA06, Wang98f]
GO:0005829 - cytosol
GO:0043234 - protein complex [GOA01a]
|MultiFun Terms:||cell processes → cell division|
|Growth Medium||Growth?||T (°C)||O2||pH||Osm/L||Growth Observations|
|LB Lennox||No||37||Aerobic||7||No [Baba06, Comment 1]|
|Mutagenesis-Variant||1 -> 32|
|Sequence-Conflict||32 -> 39|
|Mutagenesis-Variant||33 -> 49|
|Nucleotide-Phosphate-Binding-Region||103 -> 111|
|Mutagenesis-Variant||317 -> 383|
10/20/97 Gene b0095 from Blattner lab Genbank (v. M52) entry merged into EcoCyc gene EG10347; confirmed by SwissProt match.
Alexeeva10: Alexeeva S, Gadella TW, Verheul J, Verhoeven GS, den Blaauwen T (2010). "Direct interactions of early and late assembling division proteins in Escherichia coli cells resolved by FRET." Mol Microbiol 77(2);384-98. PMID: 20497333
Anderson04: Anderson DE, Gueiros-Filho FJ, Erickson HP (2004). "Assembly dynamics of FtsZ rings in Bacillus subtilis and Escherichia coli and effects of FtsZ-regulating proteins." J Bacteriol 186(17);5775-81. PMID: 15317782
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
Butland05: Butland G, Peregrin-Alvarez JM, Li J, Yang W, Yang X, Canadien V, Starostine A, Richards D, Beattie B, Krogan N, Davey M, Parkinson J, Greenblatt J, Emili A (2005). "Interaction network containing conserved and essential protein complexes in Escherichia coli." Nature 433(7025);531-7. PMID: 15690043
Carballes99: Carballes F, Bertrand C, Bouche JP, Cam K (1999). "Regulation of Escherichia coli cell division genes ftsA and ftsZ by the two-component system rcsC-rcsB." Mol Microbiol 1999;34(3);442-50. PMID: 10564486
DurandHeredia11: Durand-Heredia JM, Yu HH, De Carlo S, Lesser CF, Janakiraman A (2011). "Identification and characterization of ZapC, a stabilizer of the FtsZ ring in Escherichia coli." J Bacteriol 193(6);1405-13. PMID: 21216995
DurandHeredia12: Durand-Heredia J, Rivkin E, Fan G, Morales J, Janakiraman A (2012). "Identification of ZapD as a cell division factor that promotes the assembly of FtsZ in Escherichia coli." J Bacteriol 194(12);3189-98. PMID: 22505682
Ebersbach08: Ebersbach G, Galli E, Moller-Jensen J, Lowe J, Gerdes K (2008). "Novel coiled-coil cell division factor ZapB stimulates Z ring assembly and cell division." Mol Microbiol 68(3);720-35. PMID: 18394147
Flardh97: Flardh K, Garrido T, Vicente M (1997). "Contribution of individual promoters in the ddlB-ftsZ region to the transcription of the essential cell-division gene ftsZ in Escherichia coli." Mol Microbiol 1997;24(5);927-36. PMID: 9220001
Hale11: Hale CA, Shiomi D, Liu B, Bernhardt TG, Margolin W, Niki H, de Boer PA (2011). "Identification of Escherichia coli ZapC (YcbW) as a component of the division apparatus that binds and bundles FtsZ polymers." J Bacteriol 193(6);1393-404. PMID: 21216997
Hara97: Hara H, Yasuda S, Horiuchi K, Park JT (1997). "A promoter for the first nine genes of the Escherichia coli mra cluster of cell division and cell envelope biosynthesis genes, including ftsI and ftsW." J Bacteriol 179(18);5802-11. PMID: 9294438
Higashitani95: Higashitani A, Higashitani N, Horiuchi K (1995). "A cell division inhibitor SulA of Escherichia coli directly interacts with FtsZ through GTP hydrolysis." Biochem Biophys Res Commun 209(1);198-204. PMID: 7726836
Hu99a: Hu Z, Mukherjee A, Pichoff S, Lutkenhaus J (1999). "The MinC component of the division site selection system in Escherichia coli interacts with FtsZ to prevent polymerization." Proc Natl Acad Sci U S A 96(26);14819-24. PMID: 10611296
Justice00: Justice SS, Garcia-Lara J, Rothfield LI (2000). "Cell division inhibitors SulA and MinC/MinD block septum formation at different steps in the assembly of the Escherichia coli division machinery." Mol Microbiol 37(2);410-23. PMID: 10931335
Karimova05: Karimova G, Dautin N, Ladant D (2005). "Interaction network among Escherichia coli membrane proteins involved in cell division as revealed by bacterial two-hybrid analysis." J Bacteriol 187(7);2233-43. PMID: 15774864
Ma96a: Ma X, Ehrhardt DW, Margolin W (1996). "Colocalization of cell division proteins FtsZ and FtsA to cytoskeletal structures in living Escherichia coli cells by using green fluorescent protein." Proc Natl Acad Sci U S A 93(23);12998-3003. PMID: 8917533
Margalit04: Margalit DN, Romberg L, Mets RB, Hebert AM, Mitchison TJ, Kirschner MW, RayChaudhuri D (2004). "Targeting cell division: small-molecule inhibitors of FtsZ GTPase perturb cytokinetic ring assembly and induce bacterial lethality." Proc Natl Acad Sci U S A 101(32);11821-6. PMID: 15289600
Masuda12: Masuda H, Tan Q, Awano N, Wu KP, Inouye M (2012). "YeeU enhances the bundling of cytoskeletal polymers of MreB and FtsZ, antagonizing the CbtA (YeeV) toxicity in Escherichia coli." Mol Microbiol 84(5);979-89. PMID: 22515815
MenginLecreulx98: Mengin-Lecreulx D, Ayala J, Bouhss A, van Heijenoort J, Parquet C, Hara H (1998). "Contribution of the Pmra promoter to expression of genes in the Escherichia coli mra cluster of cell envelope biosynthesis and cell division genes." J Bacteriol 180(17);4406-12. PMID: 9721276
Mosyak00: Mosyak L, Zhang Y, Glasfeld E, Haney S, Stahl M, Seehra J, Somers WS (2000). "The bacterial cell-division protein ZipA and its interaction with an FtsZ fragment revealed by X-ray crystallography." EMBO J 19(13);3179-91. PMID: 10880432
Mukherjee98a: Mukherjee A, Cao C, Lutkenhaus J (1998). "Inhibition of FtsZ polymerization by SulA, an inhibitor of septation in Escherichia coli." Proc Natl Acad Sci U S A 95(6);2885-90. PMID: 9501185
Norris04: Norris V, Woldringh C, Mileykovskaya E (2004). "A hypothesis to explain division site selection in Escherichia coli by combining nucleoid occlusion and Min." FEBS Lett 561(1-3);3-10. PMID: 15013745
Pla91: Pla J, Sanchez M, Palacios P, Vicente M, Aldea M (1991). "Preferential cytoplasmic location of FtsZ, a protein essential for Escherichia coli septation." Mol Microbiol 5(7);1681-6. PMID: 1943703
Rajagopala14: Rajagopala SV, Sikorski P, Kumar A, Mosca R, Vlasblom J, Arnold R, Franca-Koh J, Pakala SB, Phanse S, Ceol A, Hauser R, Siszler G, Wuchty S, Emili A, Babu M, Aloy P, Pieper R, Uetz P (2014). "The binary protein-protein interaction landscape of Escherichia coli." Nat Biotechnol 32(3);285-90. PMID: 24561554
Robinson84: Robinson AC, Kenan DJ, Hatfull GF, Sullivan NF, Spiegelberg R, Donachie WD (1984). "DNA sequence and transcriptional organization of essential cell division genes ftsQ and ftsA of Escherichia coli: evidence for overlapping transcriptional units." J Bacteriol 160(2);546-55. PMID: 6094474
Romberg04: Romberg L, Mitchison TJ (2004). "Rate-limiting guanosine 5'-triphosphate hydrolysis during nucleotide turnover by FtsZ, a prokaryotic tubulin homologue involved in bacterial cell division." Biochemistry 43(1);282-8. PMID: 14705956
Salvarelli11: Salvarelli E, Krupka M, Rivas G, Vicente M, Mingorance J (2011). "Independence between GTPase active sites in the Escherichia coli cell division protein FtsZ." FEBS Lett 585(24);3880-3. PMID: 22064072
Shen09: Shen B, Lutkenhaus J (2009). "The conserved C-terminal tail of FtsZ is required for the septal localization and division inhibitory activity of MinC(C)/MinD." Mol Microbiol 72(2);410-24. PMID: 19415799
Shiomi08: Shiomi D, Margolin W (2008). "Compensation for the loss of the conserved membrane targeting sequence of FtsA provides new insights into its function." Mol Microbiol 67(3);558-69. PMID: 18186792
Trusca98: Trusca D, Scott S, Thompson C, Bramhill D (1998). "Bacterial SOS checkpoint protein SulA inhibits polymerization of purified FtsZ cell division protein." J Bacteriol 180(15);3946-53. PMID: 9683493
Vaughan04: Vaughan S, Wickstead B, Gull K, Addinall SG (2004). "Molecular evolution of FtsZ protein sequences encoded within the genomes of archaea, bacteria, and eukaryota." J Mol Evol 58(1);19-29. PMID: 14743312
Wang91: Wang XD, de Boer PA, Rothfield LI (1991). "A factor that positively regulates cell division by activating transcription of the major cluster of essential cell division genes of Escherichia coli." EMBO J 1991;10(11);3363-72. PMID: 1915297
Aldea90: Aldea M, Garrido T, Pla J, Vicente M (1990). "Division genes in Escherichia coli are expressed coordinately to cell septum requirements by gearbox promoters." EMBO J 1990;9(11);3787-94. PMID: 1698623
Ballesteros98: Ballesteros M, Kusano S, Ishihama A, Vicente M (1998). "The ftsQ1p gearbox promoter of Escherichia coli is a major sigma S-dependent promoter in the ddlB-ftsA region." Mol Microbiol 1998;30(2);419-30. PMID: 9791185
Eraso14: Eraso JM, Markillie LM, Mitchell HD, Taylor RC, Orr G, Margolin W (2014). "The Highly Conserved MraZ Protein Is a Transcriptional Regulator in Escherichia coli." J Bacteriol 196(11);2053-66. PMID: 24659771
Gohler11: Gohler AK, Kokpinar O, Schmidt-Heck W, Geffers R, Guthke R, Rinas U, Schuster S, Jahreis K, Kaleta C (2011). "More than just a metabolic regulator - elucidation and validation of new targets of PdhR in Escherichia coli." BMC Syst Biol 5(1);197. PMID: 22168595
Ishino89: Ishino F, Jung HK, Ikeda M, Doi M, Wachi M, Matsuhashi M (1989). "New mutations fts-36, lts-33, and ftsW clustered in the mra region of the Escherichia coli chromosome induce thermosensitive cell growth and division." J Bacteriol 171(10);5523-30. PMID: 2676977
Sitnikov96: Sitnikov DM, Schineller JB, Baldwin TO (1996). "Control of cell division in Escherichia coli: regulation of transcription of ftsQA involves both rpoS and SdiA-mediated autoinduction." Proc Natl Acad Sci U S A 1996;93(1);336-41. PMID: 8552633
Vinella93a: Vinella D, Joseleau-Petit D, Thevenet D, Bouloc P, D'Ari R (1993). "Penicillin-binding protein 2 inactivation in Escherichia coli results in cell division inhibition, which is relieved by FtsZ overexpression." J Bacteriol 175(20);6704-10. PMID: 8407846
Yamamoto01: Yamamoto K, Yata K, Fujita N, Ishihama A (2001). "Novel mode of transcription regulation by SdiA, an Escherichia coli homologue of the quorum-sensing regulator." Mol Microbiol 41(5);1187-98. PMID: 11555297
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