An Arg/Ala-Rich Helix in the N-Terminal Region ofM. tuberculosisFtsQ Anchors FtsZ to Membranes

AbstractMycobacteria tuberculosis (Mtb)inflicts a quarter of the worldwide population. Most drugs for treating tuberculosis target cell growth and division. With rising drug resistance, it becomes ever more urgent to better understandMtbcell division. This process begins with the formation of the Z-ring via polymerization of FtsZ and anchoring of the Z-ring to the inner membrane. Here, by combining solution and solid-state NMR spectroscopy with molecular dynamics simulations and other techniques, we show that the transmembrane protein FtsQ is a membrane anchor of theMtbZ-ring. In the otherwise disordered N-terminal cytoplasmic region of FtsQ (residues 1-99), a 29-residue, Arg/Ala-rich α-helix is formed that interacts with upstream acidic residues in solution and with acidic lipids at the membrane surface. The same helix also binds to the GTPase domain of FtsZ, with enormous implications for drug binding and Z-ring formation including its curvature.