MD Anderson Cancer Center UTHealth
Graduate School of Biomedical Sciences

Mutations Within and Between Early Cell Division Proteins and their Effects on Division Regulation in Escherichia Coli

 Kara Schoenemann, BS (Advisor: William Margolin, PhD)

          Cell division is a highly regulated process that must coordinate multiple different activities in different locations in the cell simultaneously. E. coli utilizes a macromolecular machine known as the divisome to accomplish cytokinesis. Assembly of the divisome begins with the assembly of a simpler structure known as the proto-ring. The proto-ring mainly consists of three essential proteins: FtsZ and its membrane tethers FtsA and ZipA. In this work, I aimed to understand the early regulation of division in E. coli by investigating the structure/function relationships of the proto-ring proteins, as well as their interactions with one another and how these influence the progression of division.  I found that mutations in the interaction interface between FtsA subunits change the shape of the polymer it forms, promote the assembly of FtsZ bundles, and confer gain-of-function properties in vivo. These alternative oligomeric structures support a model of early division regulation wherein the oligomerization state of the proto-ring proteins influences the progression of division. I also found that FtsA and ZipA are relatively tolerant of large deletions in their flexible linkers between their respective FtsZ-binding domains and membrane-associated domains. In particular, I found that the deletion of the proline/glutamine-rich domain in the ZipA linker enhances ZipA’s resistance to toxic FtsA overexpression, suggesting that the positioning of the Z-ring may influence the ZipA’s affinity for the C-terminal peptide of FtsZ. This work lends support to established models of cell division regulation and represents the first biological study of the disordered peptide linkers in the FtsZ membrane tethers FtsA and ZipA.

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