@article {Cohan301622, author = {Megan C. Cohan and Ammon E. Posey and Steven J. Grigsby and Anuradha Mittal and Alex S. Holehouse and Paul J. Buske and Petra A. Levin and Rohit V. Pappu}, title = {Evolved sequence features within the intrinsically disordered tail influence FtsZ assembly and bacterial cell division}, elocation-id = {301622}, year = {2018}, doi = {10.1101/301622}, publisher = {Cold Spring Harbor Laboratory}, abstract = {Intrinsically disordered regions (IDRs) challenge the well-established sequence-structure-function paradigm for describing protein function and evolution. Here, we direct a combination of biophysical and cellular studies to further our understanding of how the intrinsically disordered C-terminal tail of FtsZ contributes to cell division in rod-shaped bacteria. FtsZ is a modular protein that encompasses a conserved GTPase domain and a highly variable intrinsically disordered C-terminal tail (CTT). The CTT is essential for forming the cytokinetic Z-ring. Despite poor sequence conservation of the CTT, the patterning of oppositely charged residues, which refers to the extent of linear mixing / segregation of oppositely charged residues within CTT sequences is bounded within a narrow range. To assess the impact of evolutionary bounds on charge patterning within CTT sequences we performed experiments, aided by sequence design, to quantify the impact of changing the patterning of oppositely charged residues within the CTT on the functions of FtsZ from B. subtilis. Z-ring formation is robust if and only if the extent of linear mixing / segregation of oppositely charged residues within the CTT sequences is within evolutionarily observed bounds. Otherwise, aberrant, CTT-mediated, FtsZ assemblies impair Z-ring formation. The complexities of CTT sequences also have to be above a threshold value because FtsZ variants with low complexity CTTs are not tolerated in cells. Taken together, our results suggest that CTT sequences have evolved to be {\textquotedblleft}just right{\textquotedblright} and that this is achieved through an optimal extent of charge patterning while maintaining the sequence complexity above a threshold value.}, URL = {https://www.biorxiv.org/content/early/2018/04/14/301622}, eprint = {https://www.biorxiv.org/content/early/2018/04/14/301622.full.pdf}, journal = {bioRxiv} }