title: Biological Insights from a Simulation Model of the Critical FtsZ Accumulation Required for Prokaryotic Cell Division.
abstract: A simulation model of prokaryotic Z-ring assembly, based on the observed behavior of 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 antibacterial target. Furthermore, simulations indicate that the temperature sensitivity of the ftsZ84 mutation arises from the 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.
authors.affiliation: †Molecular Organisation and Assembly in Cells Doctoral Training Centre, Senate House, University of Warwick, Coventry CV4 7AL, United Kingdom.
authors.forename: Claire E
authors.initials: CE
authors.lastname: Dow
authors.affiliation: ‡Mathematics Institute, University of Warwick, Coventry CV4 7AL, United Kingdom.
authors.forename: Hugo A
authors.initials: HA
authors.lastname: van den Berg
authors.affiliation: §School of Life Sciences, University of Warwick, Coventry CV4 7AL, United Kingdom.
authors.forename: David I
authors.initials: DI
authors.lastname: Roper
authors.affiliation: ∥Department of Chemistry, University of Warwick, Coventry CV4 7AL, United Kingdom.|⊥Warwick Analytical Science Centre, University of Warwick, Coventry CV4 7AL, United Kingdom.
authors.forename: Alison
authors.initials: A
authors.lastname: Rodger
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002455:Cell Division; D003198:Computer Simulation; D048749:Cytokinesis; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D003599:Cytoskeleton / Q000378:metabolism; D006090:Gram-Negative Bacteria / Q000166:cytology* / Q000378:metabolism; D006094:Gram-Positive Bacteria / Q000166:cytology* / Q000378:metabolism; D008954:Models, Biological; D009154:Mutation
chemical_list: D001426:Bacterial Proteins; D003598:Cytoskeletal Proteins; C071525:FtsZ protein, Bacteria