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FtsA

From Wikipedia, the free encyclopedia
Cell division protein FtsA
E. coli cells producing FtsA-GFP, which localizes to the cell division site.
Identifiers
OrganismEscherichia coli (strain K12)
SymbolFtsA
Entrez944778
RefSeq (Prot)NP_414636.1
UniProtP0ABH0
Other data
ChromosomeGenome: 0.1 - 0.11 Mb
Search for
StructuresSwiss-model
DomainsInterPro
FtsA
Identifiers
SymbolFtsA
InterProIPR020823
SHS2 "1C" domain inserted in FtsA
Identifiers
SymbolSHS2_FtsA
PfamPF02491
InterProIPR003494
SMARTSM00842
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary

FtsA is a bacterial protein that is related to actin by overall structural similarity and in its ATP binding pocket.[1][2][3]

Along with other bacterial actin homologs such as MreB, ParM, and MamK, these proteins suggest that eukaryotic actin has a common ancestry. Like the other bacterial actins, FtsA binds ATP and can form actin-like filaments.[4] The FtsA-FtsA interface has been defined by structural as well as genetic analysis.[5] Although present in many diverse Gram-positive and Gram-negative species, FtsA is absent in actinobacteria and cyanobacteria. FtsA also is structurally similar to PilM, a type IV pilus ATPase.[6]

Function

[edit]

FtsA is required for proper cytokinesis in bacteria such as Escherichia coli, Caulobacter crescentus, and Bacillus subtilis. Originally isolated in a screen for E. coli cells that could divide at 30˚C but not at 40˚C,[7] FtsA stands for "filamentous temperature sensitive A". Many thermosensitive alleles of E. coli ftsA exist, and all map in or near the ATP binding pocket. Suppressors that restore normal function map either to the binding pocket or to the FtsA-FtsA interface.[8]

FtsA localizes to the cytokinetic ring formed by FtsZ (Z ring). One of FtsA's functions in cytokinesis is to tether FtsZ polymers to the cytoplasmic membrane via a conserved C-terminal amphipathic helix, forming an "A ring" in the process.[9] Removal of this helix results in the formation of very long and stable polymer bundles of FtsA in the cell that do not function in cytokinesis.[5] Another essential division protein, ZipA, also tethers the Z ring to the membrane and exhibits overlapping function with FtsA. FtsZ, FtsA and ZipA together are called the proto-ring because they are involved in a specific initial phase of cytokinesis.[10] Another subdomain of FtsA (2B) is required for interactions with FtsZ, via the conserved C-terminus of FtsZ.[4] Other FtsZ regulators including MinC and ZipA bind to the same C terminus of FtsZ. Finally, subdomain 1C, which is in a unique position relative to MreB and actin, is required for FtsA to recruit downstream cell division proteins such as FtsN.[11][12]

Although FtsA is essential for viability in E. coli, it can be deleted in B. subtilis. B. subtilis cells lacking FtsA divide poorly, but still survive. Another FtsZ-interacting protein, SepF (originally named YlmF; O31728), is able to replace FtsA in B. subtilis, suggesting that SepF and FtsA have overlapping functions.[13]

An allele of FtsA called FtsA* (R286W) is able to bypass the normal requirement for the ZipA in E. coli cytokinesis.[14] FtsA* also causes cells to divide at a shorter cell length than normal, suggesting that FtsA may normally receive signals from the septum synthesis machinery to regulate when cytokinesis can proceed.[15] Other FtsA*-like alleles have been found, and they mostly decrease FtsA-FtsA interactions.[5] Oligomeric state of FtsA is likely important for regulating its activity, its ability to recruit the later cell division proteins [5] and its ability to bind ATP.[8] Other cell division proteins of E. coli, including FtsN and the ABC transporter homologs FtsEX, seem to regulate septum constriction by signaling through FtsA,[16][17] and the FtsQLB subcomplex is also involved in promoting FtsN-mediated septal constriction.[18][19]

FtsA binds directly to the conserved C-terminal domain of FtsZ.[20][4] This FtsA-FtsZ interaction is likely involved in regulating FtsZ polymer dynamics. In vitro, E. coli FtsA disassembles FtsZ polymers in the presence of ATP, both in solution, as FtsA* [21] and on supported lipid bilayers.[22] E. coli FtsA itself does not assemble into detectable structures except when on membranes, where it forms dodecameric minirings that often pack in clusters and bind to single FtsZ protofilaments.[23] In contrast, FtsA* forms arcs on lipid membranes but rarely closed minirings, supporting genetic evidence that this mutant has a weaker FtsA-FtsA interface.[5] When bound to the membrane, FtsA*-like mutants, which also can form double-stranded filaments, enhance close lateral interactions between FtsZ protofilaments, in contrast to FtsA, which keeps FtsZ protofilaments apart.[24] As FtsZ protofilament bundling may be important for promoting septum formation, a switch from an FtsA-like to an FtsA*-like conformation during cell cycle progression may serve to turn on septum synthesis enzymes (FtsWI) as well as condense FtsZ polymers, setting up a positive feedback loop. In support of this model, the cytoplasmic domain of FtsN, which activates FtsWI in E. coli and interacts directly with the 1C subdomain of FtsA, switches FtsA from the miniring form to the double stranded filament form on lipid surfaces in vitro.[25] These double filaments of E. coli FtsA are antiparallel, indicating that they themselves do not treadmill like FtsZ filaments.

Although E. coli FtsA has been the most extensively studied, more is becoming understood about FtsA proteins from other species. FtsA from Streptococcus pneumoniae forms helical filaments in the presence of ATP,[26] but no interactions with FtsZ in vitro have been reported yet. FtsA colocalizes with FtsZ in S. pneumoniae, but also is required for FtsZ ring localization, in contrast to E. coli where FtsZ rings remain localized upon inactivation of FtsA. FtsA from Staphylococcus aureus forms actin-like filaments similar to those of FtsA from Thermotoga maritima. [27] In addition, S. aureus FtsA enhances the GTPase activity of FtsZ. In a liposome system, FtsA* stimulates FtsZ to form rings that can divide liposomes, mimicking cytokinesis in vitro.[28]

Structure

[edit]

Several crystal structures for FtsA are known, including a structure for E. coli FtsA.[29] Compared to MreB and eukaryotic actin, the subdomains are rearranged, and the 1B domain is swapped out for the SHS2 "1C" insert.[4][30][1][31]

References

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  1. ^ a b van den Ent F, Löwe J (Oct 2000). "Crystal structure of the cell division protein FtsA from Thermotoga maritima". The EMBO Journal. 19 (20): 5300–7. doi:10.1093/emboj/19.20.5300. PMC 313995. PMID 11032797.
  2. ^ Gunning PW, Ghoshdastider U, Whitaker S, Popp D, Robinson RC (Jun 2015). "The evolution of compositionally and functionally distinct actin filaments". Journal of Cell Science. 128 (11): 2009–19. doi:10.1242/jcs.165563. PMID 25788699.
  3. ^ Ghoshdastider U, Jiang S, Popp D, Robinson RC (Jul 2015). "In search of the primordial actin filament". Proceedings of the National Academy of Sciences of the United States of America. 112 (30): 9150–1. doi:10.1073/pnas.1511568112. PMC 4522752. PMID 26178194.
  4. ^ a b c d Szwedziak P, Wang Q, Freund SM, Löwe J (May 2012). "FtsA forms actin-like protofilaments". The EMBO Journal. 31 (10): 2249–60. doi:10.1038/emboj.2012.76. PMC 3364754. PMID 22473211.
  5. ^ a b c d e Pichoff S, Shen B, Sullivan B, Lutkenhaus J (Jan 2012). "FtsA mutants impaired for self-interaction bypass ZipA suggesting a model in which FtsA's self-interaction competes with its ability to recruit downstream division proteins". Molecular Microbiology. 83 (1): 151–67. doi:10.1111/j.1365-2958.2011.07923.x. PMC 3245357. PMID 22111832.
  6. ^ Karuppiah V, Derrick JP (Jul 2011). "Structure of the PilM-PilN inner membrane type IV pilus biogenesis complex from Thermus thermophilus". The Journal of Biological Chemistry. 286 (27): 24434–42. doi:10.1074/jbc.M111.243535. PMC 3129222. PMID 21596754.
  7. ^ Kohiyama M, Cousin D, Ryter A, Jacob F (April 1966). "Mutants thermosensibles d'Escherichia coli K12". Annales de l'Institute Pasteur. 110 (4): 465–86.
  8. ^ a b Herricks JR, Nguyen D, Margolin W (Nov 2014). "A thermosensitive defect in the ATP binding pocket of FtsA can be suppressed by allosteric changes in the dimer interface". Molecular Microbiology. 94 (3): 713–27. doi:10.1111/mmi.12790. PMC 4213309. PMID 25213228.
  9. ^ Pichoff S, Lutkenhaus J (Mar 2005). "Tethering the Z ring to the membrane through a conserved membrane targeting sequence in FtsA". Molecular Microbiology. 55 (6): 1722–34. doi:10.1111/j.1365-2958.2005.04522.x. PMID 15752196.
  10. ^ Rico AI, Krupka M, Vicente M (Jul 2013). "In the beginning, Escherichia coli assembled the proto-ring: an initial phase of division". The Journal of Biological Chemistry. 288 (29): 20830–6. doi:10.1074/jbc.R113.479519. PMC 3774354. PMID 23740256.
  11. ^ Rico AI, García-Ovalle M, Mingorance J, Vicente M (Sep 2004). "Role of two essential domains of Escherichia coli FtsA in localization and progression of the division ring". Molecular Microbiology. 53 (5): 1359–71. doi:10.1111/j.1365-2958.2004.04245.x. PMID 15387815.
  12. ^ Busiek KK, Eraso JM, Wang Y, Margolin W (Apr 2012). "The early divisome protein FtsA interacts directly through its 1c subdomain with the cytoplasmic domain of the late divisome protein FtsN". Journal of Bacteriology. 194 (8): 1989–2000. doi:10.1128/JB.06683-11. PMC 3318488. PMID 22328664.
  13. ^ Ishikawa S, Kawai Y, Hiramatsu K, Kuwano M, Ogasawara N (Jun 2006). "A new FtsZ-interacting protein, YlmF, complements the activity of FtsA during progression of cell division in Bacillus subtilis". Molecular Microbiology. 60 (6): 1364–80. doi:10.1111/j.1365-2958.2006.05184.x. PMID 16796675. S2CID 19570920.
  14. ^ Geissler B, Elraheb D, Margolin W (Apr 2003). "A gain-of-function mutation in ftsA bypasses the requirement for the essential cell division gene zipA in Escherichia coli". Proceedings of the National Academy of Sciences of the United States of America. 100 (7): 4197–202. Bibcode:2003PNAS..100.4197G. doi:10.1073/pnas.0635003100. PMC 153070. PMID 12634424.
  15. ^ Geissler B, Shiomi D, Margolin W (Mar 2007). "The ftsA* gain-of-function allele of Escherichia coli and its effects on the stability and dynamics of the Z ring". Microbiology. 153 (Pt 3): 814–25. doi:10.1099/mic.0.2006/001834-0. PMC 4757590. PMID 17322202.
  16. ^ Du S, Pichoff S, Lutkenhaus J (Aug 2016). "FtsEX acts on FtsA to regulate divisome assembly and activity". Proc Natl Acad Sci USA. 113 (34): 5052–5061. Bibcode:2016PNAS..113E5052D. doi:10.1073/pnas.1606656113. PMC 5003251. PMID 27503875.
  17. ^ Pichoff S, Du S, Lutkenhaus J (Mar 2015). "The bypass of ZipA by overexpression of FtsN requires a previously unknown conserved FtsN motif essential for FtsA-FtsN interaction supporting a model in which FtsA monomers recruit late cell division proteins to the Z ring". Molecular Microbiology. 95 (6): 971–987. doi:10.1111/mmi.12907. PMC 4364298. PMID 25496259.
  18. ^ Tsang MJ, Bernhardt TG (Mar 2015). "A role for the FtsQLB complex in cytokinetic ring activation revealed by an ftsL allele that accelerates division". Molecular Microbiology. 95 (6): 924–944. doi:10.1111/mmi.12905. PMC 4414402. PMID 25496050.
  19. ^ Liu B, Persons L, Lee L, de Boer P (Mar 2015). "Roles for both FtsA and the FtsBLQ subcomplex in FtsN-stimulated cell constriction in Escherichia coli". Molecular Microbiology. 95 (6): 945–970. doi:10.1111/mmi.12906. PMC 4428282. PMID 25496160.
  20. ^ Pichoff S, Lutkenhaus J (2002). "Unique and overlapping roles for ZipA and FtsA in septal ring assembly in Escherichia coli". EMBO Journal. 21 (4): 685–93. doi:10.1093/emboj/21.4.685. PMC 125861. PMID 11847116.
  21. ^ Beuria TK, Mullapudi S, Mileykovskaya E, Sadasivam M, Dowhan W, Margolin W (May 2009). "Adenine nucleotide-dependent regulation of assembly of bacterial tubulin-like FtsZ by a hypermorph of bacterial actin-like FtsA". The Journal of Biological Chemistry. 284 (21): 14079–86. doi:10.1074/jbc.M808872200. PMC 2682856. PMID 19297332.
  22. ^ Loose M, Mitchison TJ (Jan 2014). "The bacterial cell division proteins FtsA and FtsZ self-organize into dynamic cytoskeletal patterns". Nature Cell Biology. 16 (1): 38–46. doi:10.1038/ncb2885. PMC 4019675. PMID 24316672.
  23. ^ Krupka M, Rowlett VW, Morado D, Vitrac H, Schoenemann K, Liu J, Margolin W (July 2017). "Escherichia coli FtsA forms lipid-bound minirings that antagonize lateral interactions between FtsZ protofilaments". Nature Communications. 8: 15957. Bibcode:2017NatCo...815957K. doi:10.1038/ncomms15957. PMC 5508204. PMID 28695917.
  24. ^ Schoenemann KM, Krupka M, Rowlett VW, Distelhorst SL, Hu B, Margolin W (September 2018). "Gain-of-function variants of FtsA form diverse oligomeric structures on lipids and enhance FtsZ protofilament bundling". Molecular Microbiology. 109 (5): 676–693. doi:10.1111/mmi.14069. PMC 6181759. PMID 29995995.
  25. ^ Nierhaus T, McLaughlin SH, Bürmann F, Kureisaite-Ciziene D, Maslen SL, Skehel JM, Yu CW, Freund SM, Funke LF, Chin JW, Löwe J (September 2022). "Bacterial divisome protein FtsA forms curved antiparallel double filaments when binding to FtsN". Nature Microbiology. 7 (10): 1686–1701. doi:10.1038/s41564-022-01206-9. PMC 7613929. PMID 36123441.
  26. ^ Lara B, Rico AI, Petruzzelli S, Santona A, Dumas J, Biton J, Vicente M, Mingorance J, Massidda O (2005). "Cell division in cocci: localization and properties of the Streptococcus pneumoniae FtsA protein" (PDF). Molecular Microbiology. 55 (3): 699–711. doi:10.1111/j.1365-2958.2004.04432.x. hdl:11572/187538. PMID 15660997. S2CID 42834683.
  27. ^ Mura A, Fadda D, Perez A, Danforth ML, Musu D, Rico AI, Krupka M, Denapaite D, Tsui HT, Branny P, Vicente M, Winkler ME, Margolin W, Massidda O (February 2017). "Roles of the essential protein FtsA in cell growth and division in Streptococcus pneumoniae". Journal of Bacteriology. 199 (3): e00608-16. doi:10.1128/JB.00608-16. PMC 5237122. PMID 27872183.
  28. ^ Osawa M, Erickson HP (2013). "Liposome division by a simple bacterial division machinery". Proceedings of the National Academy of Sciences of the United States of America. 110 (27): 11000–4. Bibcode:2013PNAS..11011000O. doi:10.1073/pnas.1222254110. PMC 3703997. PMID 23776220.
  29. ^ Nierhaus T, McLaughlin SH, Bürmann F, Kureisaite-Ciziene D, Maslen SL, Skehel JM, Yu CW, Freund SM, Funke LF, Chin JW, Löwe J (September 2022). "Bacterial divisome protein FtsA forms curved antiparallel double filaments when binding to FtsN". Nature Microbiology. 7 (10): 1686–1701. doi:10.1038/s41564-022-01206-9. PMC 7613929. PMID 36123441.
  30. ^ Fujita J, Maeda Y, Nagao C, Tsuchiya Y, Miyazaki Y, Hirose M, Mizohata E, Matsumoto Y, Inoue T, Mizuguchi K, Matsumura H (May 2014). "Crystal structure of FtsA from Staphylococcus aureus". FEBS Letters. 588 (10): 1879–85. doi:10.1016/j.febslet.2014.04.008. PMID 24746687.
  31. ^ Anantharaman V, Aravind L (September 2004). "The SHS2 module is a common structural theme in functionally diverse protein groups, like Rpb7p, FtsA, GyrI, and MTH1598/TM1083 superfamilies". Proteins. 56 (4): 795–807. doi:10.1002/prot.20140. PMID 15281131. S2CID 9140384.
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