Garner, EthanMallard, William Joseph2026-01-1420252025-05-162025Mallard, William Joseph. 2025. FtsZ phosphorylation modulates tail-core binding to tune cell division in Bacillus subtilis. Doctoral Dissertation, Harvard University Graduate School of Arts and Sciences.32042133https://dash.harvard.edu/handle/1/42725391The bacterial cytoskeletal protein FtsZ orchestrates cell division in nearly all bacterial species, yet the regulatory mechanisms governing its assembly dynamics remain incompletely understood. This thesis identifies a novel intramolecular interaction within Bacillus subtilis FtsZ between its intrinsically disordered C-terminal linker (CTL) and its globular core that directly modulates FtsZ function. Through complementary biophysical, biochemical, and computational approaches, I demonstrate that the CTL specifically binds to the core’s C-terminal polymerization surface with high affinity, with residues L330-H337 forming the critical binding interface. I further establish that S333 within this region is phosphorylated in a PrkC-dependent manner, suggesting post-translational regulation of this interaction. Disruption of tail-core binding through S333 mutations produces effects across multiple biological scales: at the molecular level, it reduces FtsZ’s critical concentration and increases its GTPase activity; at the cellular level, it decreases cell length; and at the population level, it enhances growth under hypoxic and cell wall stress conditions in liquid culture while producing smaller colonies on solid media. Together, these findings suggest a previously uncharacterized regulatory mechanism where PrkC-mediated phosphorylation may dynamically tune FtsZ assembly, and consequently bacterial cell division, in response to environmental signals. This work reframes our understanding of FtsZ’s intrinsically disordered linker from an inert mechanical tether to an active regulatory element. It further highlights how phosphorylation of disordered regions can provide functional plasticity to cytoskeletal proteins.application/pdfenBacillus subtilisCell DivisionFtsZIDRBiochemistryCellular biologyMicrobiologyThesis or Dissertation2026-01-140000-0002-2271-945X