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

The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. . https://doi.org/10.1101/301622 doi: bioRxiv preprint Our findings are complimentary to those of Petrovska et al. inasmuch as filament formation weakens GTPase activity of FtsZ ( Figure 4G) . However, in the bacterial context, the weakening of enzymatic activity ensures robust FtsZ polymerization, which provides the basis for ring formation and serves as a generator of multivalency of CTP motifs that helps coordinate membrane anchoring and a network of interactions with effector proteins and regulatory molecules. The overall picture that emerges is of a multi-functional, multi-purpose CTT with definable features appear to govern the evolution of its amino acid sequence. The sequence complexity has to be sufficiently high vis-Ã -vis a random control to ensure cellular stability of FtsZ. The CTT has to enable auto-regulatory functions of suppressing GTP hydrolysis by promoting polymerization in the presence of GTP (Figure 7) . It is worth noting that polymers of FtsZ will be defined by a multivalency of CTP motifs. From a functional standpoint, this should provide the basis for membrane anchoring and mediating a full complement of protein-protein interactions. As far as cell division and cell growth are concerned, the intra-CTT sequence segregation of oppositely charged residues cannot cross a defined threshold value. If this threshold value is crossed, then the regulatory tail-mediated interactions can be overwhelmed by GTP-independent tail-to-tail interactions. These strong tail-mediated will promote alternative assemblies that compromise canonical FtsZ polymerization and Z-ring formation while conferring a dominant negative phenotype.