Exploring the structural and dynamical features of bacterial-tubulin FtsZ

Abstract

FtsZ, a bacterial tubulin, plays a crucial role in the cytokinesis process. It shares structural similarities with tubulin, as it consists of two domains—N-terminal and C-terminal domains. The protein assembles to form single-stranded protofilaments that exhibit a dynamic phenomenon known as treadmilling where the FtsZ filaments appear to execute a unidirectional movement even though individual monomers constituting the filament do not move. Despite forming protofilaments, an FtsZ molecule requires a conformational switch to form stable contacts with neighboring subunits in a filament. Therefore, FtsZ has two well-characterized conformations based on its polymerization propensity: 1) R state, preferred by the monomeric FtsZ and 2) T state, preferred by the polymeric FtsZ. The treadmilling ability of FtsZ is coupled with the conformational switch and the GTPase activity of the protein as hydrolysis-deficient mutants of FtsZ do not treadmill. We employ all-atom molecular dynamics simulations to investigate certain structural and dynamical features of the protofilaments by considering FtsZ heptamers as our model system. We simulated FtsZ filaments in three nucleotide states—GTP, GDP, and GDP-Pi—to understand the conformational states of the terminal monomers, interface dynamics of the filaments, and important interactions at the protein interdomain and interface regions. Our study reveals that the γ-phosphate binding loop T3 prompts the structural rearrangements at the interface post hydrolysis.