In the Beginning, Escherichia coli Assembled the Proto-ring: An Initial Phase of Division
2013; Elsevier BV; Volume: 288; Issue: 29 Linguagem: Inglês
10.1074/jbc.r113.479519
ISSN1083-351X
AutoresAna Isabel Rico, Marcin Krupka, Miguel Vicente,
Tópico(s)Protein Structure and Dynamics
ResumoCell division in Escherichia coli begins by assembling three proteins, FtsZ, FtsA, and ZipA, to form a proto-ring at midcell. These proteins nucleate an assembly of at least 35 components, the divisome. The structuring of FtsZ to form a ring and the processes that effect constriction have been explained by alternative but not mutually exclusive mechanisms. We discuss how FtsA and ZipA provide anchoring of the cytoplasmic FtsZ to the membrane and how a temporal sequence of alternative protein interactions may operate in the maturation and stability of the proto-ring. How the force needed for constriction is generated and how the proto-ring proteins relate to peptidoglycan synthesis remain as the main challenges for future research. Cell division in Escherichia coli begins by assembling three proteins, FtsZ, FtsA, and ZipA, to form a proto-ring at midcell. These proteins nucleate an assembly of at least 35 components, the divisome. The structuring of FtsZ to form a ring and the processes that effect constriction have been explained by alternative but not mutually exclusive mechanisms. We discuss how FtsA and ZipA provide anchoring of the cytoplasmic FtsZ to the membrane and how a temporal sequence of alternative protein interactions may operate in the maturation and stability of the proto-ring. How the force needed for constriction is generated and how the proto-ring proteins relate to peptidoglycan synthesis remain as the main challenges for future research. Cell division is the last event in the bacterial cell cycle. It takes place by producing a rigid transversal septum after the growth processes fully duplicate the contents of the cell. Septation is always preceded by segregation of the duplicated nucleoids, ensuring that each of the daughter cells contains a fully replicated chromosome. Specialized molecules control the positioning of the division machinery at midcell, preventing any harmful fragmentation that septum progression could cause on unsegregated nucleoids. The division machinery, the divisome, establishes a complex interacting network together with DNA, lipids, and peptidoglycan components. It comprises a variable number of proteins, depending on the bacterial species. These proteins have redundant multiple functions and connections serving as safeguards to complete division and to guarantee the efficiency and versatility of the process. Altogether, an efficient division process allows the proliferation of bacteria under a variety of conditions, and it is one of the reasons for their success in the environment. Free-living bacteria, such as Escherichia coli, have more elaborated divisomes, whereas those that need to grow as intracellular parasites, as such Mycoplasma genitalium, have streamlined ones (1.Glass J.I. Assad-Garcia N. Alperovich N. Yooseph S. 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Their combined action inhibits polymerization of FtsZ, blocking the assembly of the proto-ring at places other than the cell center. Nucleoid occlusion blocks septation across the nucleoid, therefore excluding a potentially harmful guillotine effect on the chromosome. In E. coli, it is accomplished by SlmA, a DNA-associated division inhibitor directly involved in preventing FtsZ polymerization in the vicinity of the nucleoid (12.Bernhardt T.G. de Boer P.A. SlmA, a nucleoid-associated, FtsZ binding protein required for blocking septal ring assembly over chromosomes in E. coli.Mol. Cell. 2005; 18: 555-564Abstract Full Text Full Text PDF PubMed Scopus (391) Google Scholar). A dimer of SlmA binds simultaneously to two molecules of FtsZ and to specific DNA sequences distributed all over the chromosome except at the Ter region. Prior to division, Ter localizes at midcell, coinciding with the site in which the FtsZ ring is assembled, and it is the last chromosomal region to segregate (13.Tonthat N.K. Arold S.T. Pickering B.F. Van Dyke M.W. Liang S. Lu Y. Beuria T.K. Margolin W. Schumacher M.A. Molecular mechanism by which the nucleoid occlusion factor, SlmA, keeps cytokinesis in check.EMBO J. 2011; 30: 154-164Crossref PubMed Scopus (123) Google Scholar, 14.Cho H. McManus H.R. Dove S.L. Bernhardt T.G. Nucleoid occlusion factor SlmA is a DNA-activated FtsZ polymerization antagonist.Proc. Natl. Acad. Sci. U.S.A. 2011; 108: 3773-3778Crossref PubMed Scopus (144) Google Scholar). The E. coli Min system comprises three proteins, MinC, MinD, and MinE. Together, they inhibit the polymerization of FtsZ at the poles and therefore prevent the production of nonviable anucleated minicells. Although with a low activity, MinC is sufficient to inhibit the assembly of FtsZ polymers (15.Shiomi D. Margolin W. 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The ribbon model proposes that FtsZ would form sufficiently long filaments to coat the internal surface of the inner membrane and assemble side-by-side as a single band. A compact ring would then be maintained by lateral contacts between filaments. The proof to support this model is that in vitro conditions favoring the elongation of and the lateral associations between protofilaments lead to the assembly of FtsZ into filaments longer than 500 nm (28.Mingorance J. Tadros M. Vicente M. González J.M. Rivas G. Vélez M. Visualization of single Escherichia coli FtsZ filament dynamics with atomic force microscopy.J. Biol. Chem. 2005; 280: 20909-20914Abstract Full Text Full Text PDF PubMed Scopus (100) Google Scholar). Such filaments have been observed when FtsZ is adsorbed onto mica surfaces, when calcium is present, or at low pH (<6.0) (29.Mateos-Gil P. Márquez I. López-Navajas P. Jiménez M. Vicente M. Mingorance J. Rivas G. Vélez M. 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In B. subtilis, in which Zap proteins are not present, a positively charged variable region found downstream of this conserved sequence mediates electrostatic interactions between FtsZ protofilaments. The equivalent region of the E. coli FtsZ protein is not charged, requiring the Zap proteins to stabilize FtsZ lateral interactions (54.Buske P.J. Levin P.A. Extreme C terminus of bacterial cytoskeletal protein FtsZ plays fundamental role in assembly independent of modulatory proteins.J. Biol. Chem. 2012; 287: 10945-10957Abstract Full Text Full Text PDF PubMed Scopus (74) Google Scholar). FtsA is an ATP-binding protein and belongs to the actin/Hsp70 superfamily (55.van den Ent F. Löwe J. Crystal structure of the cell division protein FtsA from Thermotoga maritima.EMBO J. 2000; 19: 5300-5307Crossref PubMed Scopus (167) Google Scholar). The self-interaction of FtsA is essential for the E. coli division process (56.Yim L. Vandenbussche G. Mingorance J. Rueda S. Casanova M. Ruysschaert J.M. 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When attached to a lipid monolayer, FtsA protofilaments from Thermotoga maritima (60.Szwedziak P. Wang Q. Freund S.M. Löwe J. FtsA forms actin-like protofilaments.EMBO J. 2012; 31: 2249-2260Crossref PubMed Scopus (179) Google Scholar) and E. coli (61.Martos A. Monterroso B. Zorrilla S. Reija B. Alfonso C. Mingorance J. Rivas G. Jiménez M. Isolation, characterization and lipid-binding properties of the recalcitrant FtsA division protein from Escherichia coli.PLoS ONE. 2012; 7: e39829Crossref PubMed Scopus (25) Google Scholar) undergo a conformational change, forming straight tubular structures. A short C-terminal amphipathic helix in FtsA is responsible for its attachment to the membrane (6.Pichoff S. Lutkenhaus J. Tethering the Z ring to the membrane through a conserved membrane targeting sequence in FtsA.Mol. Microbiol. 2005; 55: 1722-1734Crossref PubMed Scopus (328) Google Scholar), and it also diminishes self-interaction (56.Yim L. Vandenbussche G. Mingorance J. Rueda S. Casanova M. Ruysschaert J.M. Vicente M. Role of the carboxy terminus of Escherichia coli FtsA in self-interaction and cell division.J. Bacteriol. 2000; 182: 6366-6373Crossref PubMed Scopus (49) Google Scholar). Gene constructs engineered in E. coli to produce FtsA-FtsA in tandem result in FtsZ polymers being retained at the cell poles after septation, suggesting that the dimerization or oligomerization of FtsA modifies the stability of FtsZ polymers and promotes Z ring integrity (62.Shiomi D. Margolin W. Dimerization or oligomerization of the actin-like FtsA protein enhances the integrity of the cytokinetic Z ring.Mol. Microbiol. 2007; 66: 1396-1415PubMed Google Scholar). FtsZ is proposed to be involved in FtsA dimerization given that FtsA crystallizes as a dimer when the FtsZ C-terminal peptide is bound to FtsA but as a monomer when the FtsZ peptide is absent (55.van den Ent F. Löwe J. 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