Activation of cell division protein FtsZ -: Control of switch loop T3 conformation by the nucleotide γ-phosphate

The effect of bound nucleotide on the conformation of cell division protein FtsZ from Methanococcus jannaschii has been investigated using molecular dynamics and site-directed mutagenesis, The molecular dynamics indicate that the gamma -phosphate of GTP induces a conformational perturbation in loop T3 (Gly(88)-Gly(99) segment), in a position structurally equivalent to switch II of Ha-ras-p21, In the simulated GTP-bound state, loop T3 is pulled by the gamma -phosphate into a more compact conformation than with GDP, related to that observed in the homologous proteins alpha- and beta -tubulin, The existence of a nucleotide-induced structural change in loop T3 has been confirmed by mutating Thr(92) into Trp (T92W-W319Y FtsZ), This tryptophan (12 Angstrom away from gamma -phosphate) shows large differences in fluorescence emission, depending on which nucleotide is bound to FtsZ monomers, Loop T3 is located at a side of the contact interface between two FtsZ monomers in the current model of FtsZ filament. Such a structural change may bend the GDP filament upon hydrolysis by pushing against helix HS of next monomer, thus, generating force on the membrane during cell division. A related curvature mechanism may operate in tubulin activation.