Probing the conformational flexibility of monomeric FtsZ in GTP-bound, GDP-bound, and nucleotide-free states.

The mechanism of nucleotide-regulated assembly and disassembly of the prokaryotic cell division protein FtsZ is not yet clearly understood. In this work, we attempt to characterize the functional motions in monomeric FtsZ through molecular dynamics simulations and essential dynamics (ED) analyses and correlate those motions to FtsZ assembly and disassembly. Results suggest that the nucleotide binding subdomain of FtsZ can switch between multitudes of curved conformations in all nucleotide states, but it prefers to be in an assembly competent less curved conformation in the GTP-bound state. Further, the GDP to GTP exchange invokes a subtle conformational change in the nucleotide binding pocket that tends to align the top portion of core helix H7 along the longitudinal axis of the protein. ED analyses suggest that the longitudinal movements of H7 and the adjacent H6-H7 region modulate the motions of C-domain elements coherently. These longitudinal movements of functionally relevant H7, H6-H7, T3, T7, and H10 regions are likely to facilitate the assembly of GTP-FtsZ into straight filament. On the other hand, the observed radial or random movements of FtsZ residues in the GDP state might not allow the monomers to assemble as efficiently as GTP-bound monomers and could produce curved filaments. Our results correlate very well with recent mutagenesis data that inferred FtsZ conformational flexibility and the involvement of the H6-H7 region in assembly.