|Gene:||ftsK||Accession Numbers: G6464 (EcoCyc), b0890, ECK0881|
FtsK is an essential cell division protein linking cell division and chromosome segregation [Kennedy08]. FtsK segregates the terminus region of sister chromosomes [Stouf13]. It acts as a DNA translocase at the division site and is required for unlinking chromosome dimers.
FtsK colocalizes with FtsZ to the septal ring structure; localization is dependent on FtsZ, FtsA and ZipA, but not FtsI and FtsQ [Yu98, Wang98f, Pichoff02]. Conversely, FtsQ, FtsL and FtsI require FtsK for localization to the Z ring [Chen01d]. The FtsK protein domains involved in the interactions with other cell division proteins have been mapped [Grenga08]. When FtsK is overexpressed, Z ring formation and cell division are inhibited [Draper98].
Although the hierarchy of dependency in the assembly of cell division proteins is largely linear, recent results showed that assembly of the cell division machinery is complex [Goehring05, Goehring06]. The requirement for FtsK for localization of FtsI is indirect [Geissler05]. Overexpression of FtsN partially restores localization of FtsL and FtsQ in the absence of FtsK [Goehring07].
The FtsK protein is very large, and its membrane and cytoplasmic domains appear to have separable functions during cell division [Bigot04]. The N-terminal domain of FtsK, spanning ~200 amino acids, is sufficient for targeting FtsK to the septum [Yu98] and for its function in cell division [Draper98, Wang98f]. This domain shares some functional overlap with FtsQ, FtsB, FtsA, ZipA and FtsN and may be involved in the stability of the division protein machinery [Geissler05]. It contains four transmembrane helices linking two periplasmic loops, one of which contains a zinc metalloprotease consensus sequence that may [Dorazi00] or may not [Berezuk14] be required for function of FtsK. Refinement of FtsK membrane topology has revealed the presence of a periplasmic loop between TM3 and TM4 that is required for FtsK function [Berezuk14]. The N-terminal domain is sufficient for hexamerization of FtsN at midcell [Bisicchia13]. As long as it is targeted to the cell division septum, a truncated form of FtsK that lacks all transmembrane segments still functions in the resolution of chromosome dimers, indicating that DNA does not need to be transported through a pore formed by the transmembrane helices [Dubarry10].
Following the N-terminal membrane domain is a ~500 residue cytoplasmic linker region which may function in stabilizing the interactions of FtsK with other cell division proteins [Bigot04]. Two regions within this domain, 179-331 and 332-641, independently interact with FtsZ, FtsQ, FtsL and FtsI and were found to be required for normal septation [Dubarry10a].
The C-terminal domain of ~500 amino acids is cytoplasmic and involved in septation and chromosome partitioning [Liu98e, Yu98a, Steiner99]. It can be separated into three domains, α, β and γ [Massey06]. The αβ domain contains a nucleotide binding motif belonging to the AAA family of ATPases [Begg95] and has ATP-dependent DNA translocase activity [Aussel02, Saleh04], which has been observed in single molecule assays [Pease05, Saleh05]. The translocation step size is ~2 bp per ATP [Graham10]. The chromosomal domain within which FtsK acts has been identified [Corre05, Deghorain11]. DNA translocation by FtsK is directional and is guided by octameric sequences (known as KOPS - FtsK Orienting Polar Sequences - in E. coli) [Bigot05, Levy05, Bigot06]. The γ domain is a DNA-binding winged-helix domain that recognizes KOPS [Sivanathan06]. KOPS appear to act only as FtsK loading sites and are not read during DNA translocation [Graham10]. Real-time imaging of FtsK activity showed that KOPS binding does not involve scanning along the DNA, and is enhanced in the presence of ADP and inhibited by ATP [Lee12c]. Failure to recognize KOPS has little effect in wild type E. coli, but more serious consequences in cell populations where chromosome dimers occur more frequently [Sivanathan09].
Although FtsK can displace proteins from DNA, DNA translocation by FtsK stops at XerCD-dif sites [Graham10a]. FtsK's DNA translocation activity and its ability to displace roadblocks on DNA can be separated [Crozat10]. Single-molecule real time imaging showed that, depending on their relative binding affinity, FtsK can push, displace, or bypass many other DNA-bound proteins. In contrast, an orientation-specific interaction between FtsK and XerD causes reversal of FtsK and prevents XerCD removal. Collision with RecBCD leads to reversal or displacement of FtsK, indicating that RecBCD is a more powerful motor protein than FtsK [Lee14b].
Recombination between sister chromosomes causes formation of chromosome dimers, which must be resolved by XerCD-mediated recombination between dif sites. The C-terminal domain of FtsK is required for this activity, activating the recombinase and actively positioning the dif sites [Aussel02, Capiaux02, Massey04, Yates06]. In particular, the γ regulatory subdomain activates the formation of a Holliday junction intermediate by XerD; it is proposed that this activation of unlinking is normally coupled to the translocation function of FtsK [Grainge11]. Single-molecule techniques have allowed observation of the activation of XerCD-dif recombination by FtsK [Zawadzki13, Diagne14]. A topological mechanism for the unlinking reaction has been proposed [Shimokawa13].
Newly replicated chromosomes are topologically linked and must be decatenated by Topo IV before they can be physically separated. FtsK and Topo IV interact physically via the ParC subunit of Topo IV. Functionally, the C-terminal domain of FtsK stimulates the decatenation activity of Topo IV on positively supercoiled DNA [Espeli03, Bigot10], but not the activity of DNA gyrase [Espeli03]. Unlinking of chromosomes can also be accomplished by step-wise XerCD-dif recombination in the presence of chromosomal translocation by FtsK [Grainge07]. Unexpectedly, FtsK antagonizes Ter-induced recombination [Louarn07].
The crystal structure of a monomeric point mutant of the motor domain has been solved at 2.7 Å resolution [Massey06], and a solution structure of the γ winged-helix domain was obtained [Sivanathan06].
The cell division defect of an ftsK ts mutant, but not a deletion mutant, can be suppressed specifically by deletion of dacA, which encodes PBP5 (peptidoglycan-modifying D-alanine:D-alanine carboxypeptidase) [Begg95, Draper98]. A deletion of ftsK can be partially suppressed by overproduction of FtsN [Draper98].
ftsK expression is increased as part of the SOS response, conferring increased resistance to DNA damage [Wang98f].
Locations: inner membrane
|Map Position: [932,447 -> 936,436] (20.1 centisomes, 72°)||Length: 3990 bp / 1329 aa|
Molecular Weight of Polypeptide: 146.66 kD (from nucleotide sequence)
Unification Links: ASAP:ABE-0003027 , DIP:DIP-9703N , EchoBASE:EB3016 , EcoGene:EG13226 , EcoliWiki:b0890 , Mint:MINT-1261773 , ModBase:P46889 , OU-Microarray:b0890 , PortEco:ftsK , PR:PRO_000022719 , Pride:P46889 , Protein Model Portal:P46889 , RefSeq:NP_415410 , RegulonDB:G6464 , SMR:P46889 , String:511145.b0890 , UniProt:P46889
Relationship Links: InterPro:IN-FAMILY:IPR002543 , InterPro:IN-FAMILY:IPR018541 , InterPro:IN-FAMILY:IPR025199 , InterPro:IN-FAMILY:IPR027417 , PDB:Structure:2IUS , PDB:Structure:2J5P , Pfam:IN-FAMILY:PF01580 , Pfam:IN-FAMILY:PF09397 , Pfam:IN-FAMILY:PF13491 , Prosite:IN-FAMILY:PS50901 , Smart:IN-FAMILY:SM00843
|Biological Process:||GO:0000920 - cell separation after cytokinesis
GO:0006970 - response to osmotic stress [Diez97]
GO:0007059 - chromosome segregation [UniProtGOA11a, GOA01a, Graham10a, Grainge07, Capiaux02, Yu98a]
GO:0008152 - metabolic process [Bigot10, Graham10a, Bonne09, Lowe08, Massey06, Levy05]
GO:0009651 - response to salt stress [Diez97]
GO:0043085 - positive regulation of catalytic activity [Grainge11]
GO:0045893 - positive regulation of transcription, DNA-templated [Diez97]
GO:0051301 - cell division [UniProtGOA11a, GOA01a, Dubarry10a, Yu98a, Draper98, Diez97, Begg95]
GO:0071236 - cellular response to antibiotic [Wang98f]
GO:0007049 - cell cycle [UniProtGOA11a, GOA01a]
|Molecular Function:||GO:0003677 - DNA binding
[UniProtGOA11a, GOA01a, Lowe08]
GO:0005515 - protein binding [DUlisse07, Grenga08]
GO:0015616 - DNA translocase activity [Graham10a, Bonne09, Levy05]
GO:0016887 - ATPase activity [Bigot10, Graham10a, Lowe08]
GO:0033676 - double-stranded DNA-dependent ATPase activity [Massey06]
GO:0042802 - identical protein binding [Bisicchia13]
GO:0043565 - sequence-specific DNA binding [Sivanathan06, Ptacin06]
GO:0000166 - nucleotide binding [UniProtGOA11a]
GO:0005524 - ATP binding [UniProtGOA11a, GOA01a]
|Cellular Component:||GO:0005886 - plasma membrane
[UniProtGOA11, UniProtGOA11a, DiazMejia09, Daley05, Dorazi00]
GO:0005887 - integral component of plasma membrane [Dorazi00]
GO:0016020 - membrane [UniProtGOA11a, Wang98f, Dorazi00]
GO:0016021 - integral component of membrane [UniProtGOA11a, GOA01a]
|MultiFun Terms:||cell processes → cell division|
|cell processes → SOS response|
|cell structure → membrane|
|transport → Transporters of Unknown Classification|
|Growth Medium||Growth?||T (°C)||O2||pH||Osm/L||Growth Observations|
|LB enriched||Yes||37||Aerobic||6.95||Yes [Gerdes03, Comment 1]|
|LB Lennox||No||37||Aerobic||7||No [Baba06, Comment 2]|
|Transmembrane-Region||25 -> 44|
|Transmembrane-Region||75 -> 98|
|Transmembrane-Region||116 -> 132|
|Transmembrane-Region||163 -> 179|
|Protein-Segment||184 -> 817|
|Protein-Segment||331 -> 822|
|Sequence-Conflict||333 -> 334|
|Sequence-Conflict||388 -> 389|
|Protein-Segment||818 -> 943|
|Protein-Segment||944 -> 1258|
|Conserved-Region||974 -> 1187|
|Nucleotide-Phosphate-Binding-Region||994 -> 999|
|Sequence-Conflict||1101 -> 1103|
|Protein-Segment||1259 -> 1329|
Markus Krummenacker on Tue Oct 14, 1997:
Gene object created from Blattner lab Genbank (v. M52) entry.
Aussel02: Aussel L, Barre FX, Aroyo M, Stasiak A, Stasiak AZ, Sherratt D (2002). "FtsK Is a DNA motor protein that activates chromosome dimer resolution by switching the catalytic state of the XerC and XerD recombinases." Cell 108(2);195-205. PMID: 11832210
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
Berezuk14: Berezuk AM, Goodyear M, Khursigara CM (2014). "Site-directed fluorescence labeling reveals a revised N-terminal membrane topology and functional periplasmic residues in the Escherichia coli cell division protein FtsK." J Biol Chem. PMID: 25002583
Bigot04: Bigot S, Corre J, Louarn JM, Cornet F, Barre FX (2004). "FtsK activities in Xer recombination, DNA mobilization and cell division involve overlapping and separate domains of the protein." Mol Microbiol 54(4);876-86. PMID: 15522074
Bigot05: Bigot S, Saleh OA, Lesterlin C, Pages C, El Karoui M, Dennis C, Grigoriev M, Allemand JF, Barre FX, Cornet F (2005). "KOPS: DNA motifs that control E. coli chromosome segregation by orienting the FtsK translocase." EMBO J 24(21);3770-80. PMID: 16211009
Bisicchia13: Bisicchia P, Steel B, Mariam Debela MH, Lowe J, Sherratt D (2013). "The N-terminal membrane-spanning domain of the Escherichia coli DNA translocase FtsK hexamerizes at midcell." MBio 4(6);e00800-13. PMID: 24302254
Crozat10: Crozat E, Meglio A, Allemand JF, Chivers CE, Howarth M, Venien-Bryan C, Grainge I, Sherratt DJ (2010). "Separating speed and ability to displace roadblocks during DNA translocation by FtsK." EMBO J 29(8);1423-33. PMID: 20379135
Deghorain11: Deghorain M, Pages C, Meile JC, Stouf M, Capiaux H, Mercier R, Lesterlin C, Hallet B, Cornet F (2011). "A defined terminal region of the E. coli chromosome shows late segregation and high FtsK activity." PLoS One 6(7);e22164. PMID: 21799784
Diagne14: Diagne CT, Salhi M, Crozat E, Salome L, Cornet F, Rousseau P, Tardin C (2014). "TPM analyses reveal that FtsK contributes both to the assembly and the activation of the XerCD-dif recombination synapse." Nucleic Acids Res 42(3);1721-32. PMID: 24214995
DiazMejia09: Diaz-Mejia JJ, Babu M, Emili A (2009). "Computational and experimental approaches to chart the Escherichia coli cell-envelope-associated proteome and interactome." FEMS Microbiol Rev 33(1);66-97. PMID: 19054114
Diez97: Diez AA, Farewell A, Nannmark U, Nystrom T (1997). "A mutation in the ftsK gene of Escherichia coli affects cell-cell separation, stationary-phase survival, stress adaptation, and expression of the gene encoding the stress protein UspA." J Bacteriol 179(18);5878-83. PMID: 9294448
DUlisse07: D'Ulisse V, Fagioli M, Ghelardini P, Paolozzi L (2007). "Three functional subdomains of the Escherichia coli FtsQ protein are involved in its interaction with the other division proteins." Microbiology 153(Pt 1);124-38. PMID: 17185541
Geissler05: Geissler B, Margolin W (2005). "Evidence for functional overlap among multiple bacterial cell division proteins: compensating for the loss of FtsK." Mol Microbiol 58(2);596-612. PMID: 16194242
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
Goehring05: Goehring NW, Gueiros-Filho F, Beckwith J (2005). "Premature targeting of a cell division protein to midcell allows dissection of divisome assembly in Escherichia coli." Genes Dev 19(1);127-37. PMID: 15630023
Goehring06: Goehring NW, Gonzalez MD, Beckwith J (2006). "Premature targeting of cell division proteins to midcell reveals hierarchies of protein interactions involved in divisome assembly." Mol Microbiol 61(1);33-45. PMID: 16824093
Graham10: Graham JE, Sherratt DJ, Szczelkun MD (2010). "Sequence-specific assembly of FtsK hexamers establishes directional translocation on DNA." Proc Natl Acad Sci U S A 107(47);20263-8. PMID: 21048089
Grenga08: Grenga L, Luzi G, Paolozzi L, Ghelardini P (2008). "The Escherichia coli FtsK functional domains involved in its interaction with its divisome protein partners." FEMS Microbiol Lett 287(2);163-7. PMID: 18759781
Lee12c: Lee JY, Finkelstein IJ, Crozat E, Sherratt DJ, Greene EC (2012). "Single-molecule imaging of DNA curtains reveals mechanisms of KOPS sequence targeting by the DNA translocase FtsK." Proc Natl Acad Sci U S A 109(17);6531-6. PMID: 22493241
Lee14b: Lee JY, Finkelstein IJ, Arciszewska LK, Sherratt DJ, Greene EC (2014). "Single-molecule imaging of FtsK translocation reveals mechanistic features of protein-protein collisions on DNA." Mol Cell 54(5);832-43. PMID: 24768536
Lesterlin08: Lesterlin C, Pages C, Dubarry N, Dasgupta S, Cornet F (2008). "Asymmetry of chromosome Replichores renders the DNA translocase activity of FtsK essential for cell division and cell shape maintenance in Escherichia coli." PLoS Genet 4(12);e1000288. PMID: 19057667
Levy05: Levy O, Ptacin JL, Pease PJ, Gore J, Eisen MB, Bustamante C, Cozzarelli NR (2005). "Identification of oligonucleotide sequences that direct the movement of the Escherichia coli FtsK translocase." Proc Natl Acad Sci U S A 102(49);17618-23. PMID: 16301526
Lowe08: Lowe J, Ellonen A, Allen MD, Atkinson C, Sherratt DJ, Grainge I (2008). "Molecular mechanism of sequence-directed DNA loading and translocation by FtsK." Mol Cell 31(4);498-509. PMID: 18722176
Saleh05: Saleh OA, Bigot S, Barre FX, Allemand JF (2005). "Analysis of DNA supercoil induction by FtsK indicates translocation without groove-tracking." Nat Struct Mol Biol 12(5);436-40. PMID: 15821742
Shimokawa13: Shimokawa K, Ishihara K, Grainge I, Sherratt DJ, Vazquez M (2013). "FtsK-dependent XerCD-dif recombination unlinks replication catenanes in a stepwise manner." Proc Natl Acad Sci U S A 110(52);20906-11. PMID: 24218579
Sivanathan06: Sivanathan V, Allen MD, de Bekker C, Baker R, Arciszewska LK, Freund SM, Bycroft M, Lowe J, Sherratt DJ (2006). "The FtsK gamma domain directs oriented DNA translocation by interacting with KOPS." Nat Struct Mol Biol 13(11);965-72. PMID: 17057717
Sivanathan09: Sivanathan V, Emerson JE, Pages C, Cornet F, Sherratt DJ, Arciszewska LK (2009). "KOPS-guided DNA translocation by FtsK safeguards Escherichia coli chromosome segregation." Mol Microbiol 71(4);1031-42. PMID: 19170870
Yates06: Yates J, Zhekov I, Baker R, Eklund B, Sherratt DJ, Arciszewska LK (2006). "Dissection of a functional interaction between the DNA translocase, FtsK, and the XerD recombinase." Mol Microbiol 59(6);1754-66. PMID: 16553881
Yu98: Yu XC, Tran AH, Sun Q, Margolin W (1998). "Localization of cell division protein FtsK to the Escherichia coli septum and identification of a potential N-terminal targeting domain." J Bacteriol 180(5);1296-304. PMID: 9495771
Zawadzki13: Zawadzki P, May PF, Baker RA, Pinkney JN, Kapanidis AN, Sherratt DJ, Arciszewska LK (2013). "Conformational transitions during FtsK translocase activation of individual XerCD-dif recombination complexes." Proc Natl Acad Sci U S A 110(43);17302-7. PMID: 24101525
Lewis92: Lewis LK, Jenkins ME, Mount DW (1992). "Isolation of DNA damage-inducible promoters in Escherichia coli: regulation of polB (dinA), dinG, and dinH by LexA repressor." J Bacteriol 174(10);3377-85. PMID: 1577702
Lewis94: Lewis LK, Harlow GR, Gregg-Jolly LA, Mount DW (1994). "Identification of high affinity binding sites for LexA which define new DNA damage-inducible genes in Escherichia coli." J Mol Biol 241(4);507-23. PMID: 8057377
©2015 SRI International, 333 Ravenswood Avenue, Menlo Park, CA 94025-3493