The interaction of FtsZ with itself, GTP, and FtsA was examined by analyzing the sensitivity of FtsZ to proteolysis and by using the yeast two-hybrid system. The N-terminal conserved domain consisting of 320 amino acids bound GTP, and a central region of FtsZ, encompassing slightly more than half of the protein, was cross-linked to GTP. Site-directed mutagenesis revealed that none of six highly conserved aspartic acid and asparagine residues were required for GTP binding. These results indicate that the specificity determinants for GTP binding are different than those for the GTPase superfamily. The N-terminal conserved domain of FtsZ contained a site for self-interaction that is conserved between FtsZ proteins from distantly related bacterial species. FtsZ 320 , which was truncated at the end of the conserved domain, was a potent inhibitor of division although it expressed normal GTPase activity and could polymerize. FtsZ was also found to interact directly with FtsA, and this interaction could also be observed between these proteins from distantly related bacterial species.

The interaction between inhibitors of cell division and FtsZ were assessed by using the yeast two-hybrid system. An interaction was observed between FtsZ and SulA, a component of the SOS response, and the interacting regions were mapped to their conserved domains. This interaction was reduced by mutations in sulA and by most mutations in ftsZ that make cell refractory to sulA. No interaction was detected between FtsZ and MinCD, an inhibitory component of the site selection system. However, interactions were observed among various members of the Min system, and MinE was found to reduce the interaction between MinC and MinD. The implications of these findings for cell division are discussed.Cell division in bacteria is a complex process involving spatial and temporal regulation of the formation of the septum (reviewed in reference 11). The earliest defined step is the assembly of FtsZ, an essential cell division protein (8), into a ring at the future division site (4). The FtsZ protein has GTPase activity (10, 32, 37) and can assemble in vitro to form protein filaments (7,15,33). It has been suggested that the assembly of the FtsZ ring occurs through self-assembly involving a GTP cycle and is a key regulated step during cell division (25). Several inhibitors of cell division, SulA, a component of the SOS response, and MinCD, involved in selection of the division site, prevent formation of the FtsZ ring (6).As a component of the SOS response, SulA is induced following damage to DNA (21). It is an unstable protein and is degraded primarily by a protease encoded by the lon gene (31). As a result, lon mutants are hypersensitive to DNA damage, as the induction of SulA leads to a lethal filamentation (19). In wild-type cells, induction of SulA by DNA damage leads to filamentation which is readily reversed after the inducing signal dissipates. This inhibition of division by SulA is readily reversible, even in the absence of protein synthesis, arguing that SulA does not irreversibly inactivate the cell division machinery (29).MinCD is a more complex inhibitor of cell division, as its activity is spatially regulated by a third component, MinE (12). MinC is thought to be the component of the inhibitor that interacts with the division machinery, since overproduction of MinC alone can lead to division inhibition (14) and MinC can combine with another partner, DicB, to become an efficient inhibitor (13,23,35). Since MinE can regulate MinCD but not MinC overproduction or the MinCDicB combination, it is thought that it acts through MinD (14).There is genetic and biochemical evidence suggesting that FtsZ is the target of SulA and MinCD. Overproduction of FtsZ suppresses the lethal filamentation caused by SulA or MinCD (13, 26), and mutations, selected as resistant to SulA, map to the ftsZ gene (2, 24). These mutations, particularly ftsZ2, also show increased resistance to MinCD (3). At least two of these mutations, ftsZ114 and ftsZ9, result in an increased degradation rate of SulA that has been interpreted as a decreased interact...

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This paper considers a class of mean field linear-quadratic-Gaussian (LQG) games with model uncertainty. The drift term in the dynamics of the agents contains a common unknown function. We take a robust optimization approach where a representative agent in the limiting model views the drift uncertainty as an adversarial player. By including the mean field dynamics in an augmented state space, we solve two optimal control problems sequentially, which combined with consistent mean field approximations provides a solution to the robust game. A set of decentralized control strategies is derived by use of forward-backward stochastic differential equations (FBSDE) and shown to be a robust ε-Nash equilibrium.

We consider a class of linear-quadratic-Gaussian mean-field games with a major agent and considerable heterogeneous minor agents in the presence of mean-field interactions. The individual admissible controls are constrained in closed convex subsets Γ k of R m . The decentralized strategies for individual agents and consistency condition system are represented in an unified manner through a class of mean-field forward-backward stochastic differential equations involving projection operators on Γ k . The well-posedness of consistency system is established in both the local and global cases by the contraction mapping and discounting method respectively. Related ε−Nash equilibrium property is also verified.