Assembly of cell division proteins at the E. coli cell center

Buddelmeijer, Nienke; Beckwith, Jon

doi:10.1016/s1369-5274(02)00374-0

Cited by 123 publications

(133 citation statements)

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“…B acterial cells divide by binary fission, a process that involves invagination of the cell envelope at the division site to form a septum. The earliest known step in bacterial cytokinesis is the assembly of the essential division protein FtsZ into the contractile Z ring on the inner face of the cytoplasmic membrane at the site of division (1)(2)(3). Another 12 proteins in Escherichia coli then congregate at the Z ring in a sequentially dependent pathway, causing assembly of the septal ring that guides circumferential septum synthesis (2)(3)(4)(5).…”

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confidence: 99%

Targeting cell division: Small-molecule inhibitors of FtsZ GTPase perturb cytokinetic ring assembly and induce bacterial lethality

Margalit

Romberg

Mets

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

195

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FtsZ, the ancestral homolog of eukaryotic tubulins, is a GTPase that assembles into a cytokinetic ring structure essential for cell division in prokaryotic cells. Similar to tubulin, purified FtsZ polymerizes into dynamic protofilaments in the presence of GTP; polymer assembly is accompanied by GTP hydrolysis. We used a high-throughput protein-based chemical screen to identify small molecules that target assembly-dependent GTPase activity of FtsZ. Here, we report the identification of five structurally diverse compounds, named Zantrins, which inhibit FtsZ GTPase either by destabilizing the FtsZ protofilaments or by inducing filament hyperstability through increased lateral association. These two classes of FtsZ inhibitors are reminiscent of the antitubulin drugs colchicine and Taxol, respectively. We also show that Zantrins perturb FtsZ ring assembly in Escherichia coli cells and cause lethality to a variety of bacteria in broth cultures, indicating that FtsZ antagonists may serve as chemical leads for the development of new broad-spectrum antibacterial agents. Our results illustrate the utility of small-molecule chemical probes to study FtsZ polymerization dynamics and the feasibility of FtsZ as a novel therapeutic target

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mentioning

confidence: 99%

Targeting cell division: Small-molecule inhibitors of FtsZ GTPase perturb cytokinetic ring assembly and induce bacterial lethality

Margalit

Romberg

Mets

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

195

202

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“…In Escherichia coli the known divisomal proteins are thought to be recruited to the division site in the following hierarchical order: FtsZ4ZipA,FtsA4FtsEX4FtsK4FtsQ4(FtsL, FtsB)4FtsW4FtsI 4FtsN4AmiC, where the arrow indicates that recruitment of a particular protein requires prior assembly of all previously listed components, and parentheses enclose proteins whose recruitment to the divisome is interdependent (2,9,10). However, recent studies suggest that some subcomplexes, such as that formed among FtsQ, FtsL, and FtsB, might be preassembled before Z ring formation and trafficked to the developing division site as a preformed complex (2,11).…”

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confidence: 99%

Domain architecture and structure of the bacterial cell division protein DivIB

Robson

King²

2006

Proc. Natl. Acad. Sci. U.S.A.

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Bacterial cytokinesis requires the coordinated assembly of a complex of proteins, collectively known as the divisome, at the incipient division site. DivIB͞FtsQ is a conserved component of the divisome in bacteria with cell walls, suggesting that it plays a role in synthesis and͞or remodeling of septal peptidoglycan. We demonstrate that the extracytoplasmic region of DivIB comprises three discrete domains that we designate ␣, ␤, and ␥ from the N to C terminus. The ␣-domain is proximal to the cytoplasmic membrane and coincident with the polypeptide transport-associated domain that was proposed previously to function as a molecular chaperone. The ␤-domain has a unique 3D fold, with no eukaryotic counterpart, and we show that it interconverts between two discrete conformations via cis-trans isomerization of a Tyr-Pro peptide bond. We propose that this isomerization might modulate protein-protein interactions of the flanking ␣-and ␥-domains. The C-terminal ␥-domain is unstructured in the absence of other divisomal proteins, but we show that it is critical for DivIB function.bacterial cytokinesis ͉ divisome ͉ NMR ͉ protein structure B acterial cytokinesis requires spatiotemporal coordination of the assembly of a complex of cell division proteins, collectively known as the divisome, at the incipient division site (1, 2). Divisome assembly is initiated by the formation of a circumferential ring of FtsZ (the Z ring) around the inner surface of the cytoplasmic membrane (3, 4). FtsZ, the precursor of eukaryotic tubulin, is a GTPase that most likely provides at least part of the contractile force for septal invagination through dynamic remodeling of the Z ring (5-7). In addition, the Z ring promotes the switch from lateral to preseptal murein synthesis (8), and it provides a scaffold for recruitment of downstream divisomal proteins.In Escherichia coli the known divisomal proteins are thought to be recruited to the division site in the following hierarchical order: FtsZ4ZipA,FtsA4FtsEX4FtsK4FtsQ4(FtsL, FtsB)4FtsW4FtsI 4FtsN4AmiC, where the arrow indicates that recruitment of a particular protein requires prior assembly of all previously listed components, and parentheses enclose proteins whose recruitment to the divisome is interdependent (2, 9, 10). However, recent studies suggest that some subcomplexes, such as that formed among FtsQ, FtsL, and FtsB, might be preassembled before Z ring formation and trafficked to the developing division site as a preformed complex (2, 11). This latter situation is likely more akin to that in Bacillus subtilis, where the observed interdependent localization of most divisomal proteins argues for a more concerted recruitment to the division site (1,12).Whereas the earliest recruits to the division site are either wholly or mostly cytoplasmic (e.g., FtsZ, FtsA, and FtsK), the later recruits are typically bitopic membrane proteins with a short N-terminal cytoplasmic region, a single transmembrane segment, and a larger extracytoplasmic (ec) domain (i.e., FtsQ, FtsL, FtsB, FtsI, and FtsN). Rema...

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“…Absence of interactions of some of the D. radiodurans proteins came as a surprise because such interactions are conserved in other bacteria. For example, interaction of FtsA with FtsQ has been found functionally critical in the assembly of FtsK, FtsL and FtsB components in the divisome of other bacteria (Buddelmeijer & Beckwith, 2002;Gonzalez & Beckwith, 2009 (Tables S8, S9 and S10).…”

Section: Discussionmentioning

confidence: 99%