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Journal of Bacteriology, April 2008, p. 2513-2526, Vol. 190, No. 7
0021-9193/08/$08.00+0     doi:10.1128/JB.01612-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Investigation of Regulation of FtsZ Assembly by SulA and Development of a Model for FtsZ Polymerization{triangledown} ,{dagger}

Alex Dajkovic,{ddagger} Amit Mukherjee,§ and Joe Lutkenhaus*

Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, Kansas City, Kansas 66160

Received 3 October 2007/ Accepted 21 January 2008

In Escherichia coli FtsZ organizes into a cytoskeletal ring structure, the Z ring, which effects cell division. FtsZ is a GTPase, but the free energy of GTP hydrolysis does not appear to be used for generation of the constriction force, leaving open the question of the function of the GTPase activity of FtsZ. Here we study the mechanism by which SulA, an inhibitor of FtsZ induced during the SOS response, inhibits FtsZ function. We studied the effects of SulA on the in vitro activities of FtsZ, on Z rings in vivo, and on a kinetic model for FtsZ polymerization in silico. We found that the binding of SulA to FtsZ is necessary but not sufficient for inhibition of polymerization, since the assembly of FtsZ polymers in the absence of the GTPase activity was not inhibited by SulA. We developed a new model for FtsZ polymerization that accounts for the cooperativity of FtsZ and could account for cooperativity observed in other linear polymers. When SulA was included in the kinetic scheme, simulations revealed that SulA with strong affinity for FtsZ delayed, but did not prevent, the assembly of polymers when they were not hydrolyzing GTP. Furthermore, the simulations indicated that SulA controls the assembly of FtsZ by binding to a polymerization-competent form of the FtsZ molecule and preventing it from participating in assembly. In vivo stoichiometry of the disruption of Z rings by SulA suggests that FtsZ may undergo two cooperative transitions in forming the Z ring.


* Corresponding author. Mailing address: Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, Kansas City, KS 66160. Phone: (913) 588-7054. Fax: (913) 588-7295. E-mail: jlutkenh{at}kumc.edu

{triangledown} Published ahead of print on 1 February 2008.

{dagger} Supplemental material for this article may be found at http://jb.asm.org/.

{ddagger} Present address: Institut Curie, UMR144, 12 rue Lhomond, 75005 Paris, France.

§ Present address: Division of Molecular Biology, Office of Applied Research and Safety Assessment (MOD-1), Center for Food Safety and Applied Nutrition (HFS-025), U.S. Food and Drug Administration, 8301 Muirkirk Road, Laurel, MD 20708.


Journal of Bacteriology, April 2008, p. 2513-2526, Vol. 190, No. 7
0021-9193/08/$08.00+0     doi:10.1128/JB.01612-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.




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