Biological Insights from a Simulation Model of the Critical FtsZ Accumulation Required for Prokaryotic Cell Division

Abstract

Copyright and reuse:The Warwick Research Archive Portal (WRAP) makes this work of researchers of the University of Warwick available open access under the following conditions. Copyright © and all moral rights to the version of the paper presented here belong to the individual author(s) and/or other copyright owners. To the extent reasonable and practicable the material made available in WRAP has been checked for eligibility before being made available.Copies of full items can be used for personal research or study, educational, or not-forprofit purposes without prior permission or charge. Provided that the authors, title and full bibliographic details are credited, a hyperlink and/or URL is given for the original metadata page and the content is not changed in any way. Publisher's statement:This document is the Accepted Manuscript version of a Published Work that appeared in final form in Biochemistry, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://pubs.acs.org/doi/abs/10.1021/acs.biochem.5b00261The version presented here may differ from the published version or, version of record, if you wish to cite this item you are advised to consult the publisher's version. Please see the 'permanent WRAP url' above for details on accessing the published version and note that access may require a subscription. FtsZ in vitro as well as on in vivo parameters, is used to integrate critical processes in cell division. According to the model, the cell's ability to divide depends on a "contraction parameter" (χ) that links the force of contraction to the dynamics of FtsZ. This parameter accurately predicts the outcome of division. Evaluating the GTP binding strength, the FtsZ polymerization rate, and the intrinsic GTP hydrolysis/dissociation activity, we find that inhibition of GTP-FtsZ binding is an inefficient anti-bacterial target. Furthermore, simulations indicate that the temperature sensitivity of the ftsZ84 mutation arises from the 2 conversion of FtsZ to a dual-specificity NTPase. Finally, the sensitivity to temperature of the rate of ATP hydrolysis, over the critical temperature range, leads us to conclude that the ftsZ84 mutation affects the turnover rate of the Z-ring much less strongly than previously reported.

Splitsville: structural and functional insights into the dynamic bacterial Z ring

“…Both molecular modeling 110 and FtsZ crystal structure analysis 111 also support a model where a membrane-tethered FtsZ could provide the constrictive force for membrane invagination. However, recent fluorescence recovery after photobleaching (FRAP) studies indicate that FtsZ completely disassembles prior to the completion of constriction 112 , suggesting that at least the latter stages of membrane constriction involve additional factors.…”

“…(A) The evolutionarily divergent B. subtilis and E. coli each use unrelated glucosyltransferases to coordinate growth rate with cell division through a metabolic determinant: levels of UDP-glucose 109,111,110 . For B. subtilis (left), high levels of UDP-glucose during nutrient-rich growth permits UgtP synthesize the diglucosyl-diacylglycerol (Di-glc-DAG) anchor for lipoteichoic acid (LTA), an anionic polymer that is a major component of the Gram-positive cell wall.…”

Nano-encapsulated Escherichia coli Divisome Anchor ZipA, and in Complex with FtsZ

“…In fact, it suggest that the simplistic cookie cutter visualisation of the SMALP is appropriate with the SMA wrapping around lipids and the buried portions of ZipA but leaving its hydrophilic parts exposed to enable its normal FtsZ binding activity with the bundled geometries avoiding the SMALP just as they accommodate a membrane surface. The fact that SMALP encapsulated ZipA binds to monomers indicates that the ZipA site does not span multiple FtsZ molecules, in contrast to ZapA which reduces the rate of hydrolysis facilitating longer polymers and enhanced cell division 66 which is in accord with it having no effect on GTPase activity of FtsZ 67 Based on these data we speculate that the ZipA is present in the membrane and attracts FtsZ monomers to bind. When an FtsZ molecule is incorporated into the ring, a ZipA is automatically included and ensures membrane binding.…”

Mathematical Models of Microbial Growth and Metabolism: A Whole-Organism Perspective

“…Prior to cell division, the cell elongates to approximately twice its original length while its genetic material is replicated. Once this is complete, filamentous temperature sensitive (Fts) proteins, chief among which is FtsZ, assemble to form the cell division apparatus (divisome) by polymerizing and thus forming the socalled Z-ring, which localises to the middle of the cell [37][38][39] . New cell envelope material is synthesised and the two chromosomes are pulled apart.…”