Evolved sequence features within the intrinsically disordered tail influence FtsZ assembly and bacterial cell division

Megan C. Cohan; Ammon E. Posey; Steven J. Grigsby; Anuradha Mittal; Alex S. Holehouse; Paul J. Buske; Petra A. Levin; Rohit V. Pappu

We propose that clues to the observed complexities and regulation of FtsZ assembly come from the distinctive protein architecture, which include modules other than the GTPase domain ( Figure 1A) . The modular architecture of FtsZ encompasses a folded N-terminal core domain that forms an active GTP hydrolysis site upon dimerization. The negatively charged core includes the GTP binding site and the coordinating T7 loop. The interface between the nucleotide binding site and the T7 loop (in dimers and higher order polymers) forms the active site for GTP hydrolysis (Oliva et al., 2007) . The C-terminal stretch of FtsZ includes an intrinsically disordered linker (CTL), a 17-residue C-terminal peptide (CTP), and 7-10 residue stretch that is rich in basic residues and has been designated as the C-terminal variable region or CTV Levin, 2012, 2013; Buske et al., 2015) . The CTP is an alpha-helical 7 molecular recognition element (Oldfield et al., 2005) that coordinates heterotypic protein-protein interactions involving FtsZ. The interaction partners that engage with FtsZ through the CTP include the protein FtsA, which assists in the bundling of FtsZ protofilaments and anchoring of Z-rings to bacterial membranes, and SepF, which is required for the late stages of cell division (Adams and Errington, 2009) . Depending on its charge, the CTV can play a significant role in mediating lateral interactions between FtsZ polymers in vitro and in determining the integrity of the FtsZ ring in vivo (Buske and Levin, 2012) .