NMR study of the interaction between MinC and FtsZ and modeling of the FtsZ:MinC complex.

The Min system is a key spatial regulator of cell division in rod-shaped bacteria and the first FtsZ-negative modulator to be recognized. Nevertheless, despite extensive genetic and in vitro studies, the molecular mechanism used by MinC to inhibit Z-ring formation remains incompletely understood. The crystallization of FtsZ in complex with other negative regulators such as SulA and MciZ has provided important structural information to corroborate in vitro experiments and establish the mechanism of Z-ring antagonism by these modulators. However, MinC and FtsZ have so far eluded co-crystallization, probably because their complex is too unstable to be crystallized. To gain structural insight into the mechanism of action of MinC, we determined the solution structure of the N-terminal domain of Bacillus subtilis MinC, and through NMR titration experiments and mutagenesis identified the binding interfaces involved in the MinC-FtsZ interaction. By using our experimental results as restraints in docking, we also constructed a molecular model for the FtsZ:MinC complex and validated it by molecular dynamics. The model shows that MinC binding overlaps with the FtsZ polymerization interface on the C-terminal globular subdomain of FtsZ and, thus, provides a structural basis for MinC inhibition of FtsZ filament formation. Given that the C-terminal polymerization interface of FtsZ corresponds to the plus end of FtsZ filaments, we propose that capping is the main mechanism employed by MinC to antagonize FtsZ polymerization.