Cell division in most bacteria is carried out by a conserved set of essential proteins. They can be divided into those that appear absolutely essential and carry out core activities and those that appear to have been added to the core for regulatory purposes and can be bypassed by overexpression of or mutation in a core component. The core components in E. coli include the tubulin homologue FtsZ which assembles into filaments that are tethered to the membrane by FtsA. FtsA serves as a hub that recruits the enzymes, FtsW/FtsI, needed to make septal PG. In addition, to these core proteins the noncore proteins include FtsE/FtsX which regulates divisome assembly and couples septal PG synthesis to PG hydrolysis, ZipA an additional membrane tether for FtsZ, FtsK which plays a role in recruitment and DNA segregation, and FtsN which triggers septation. FtsQ/FtsL/FtsB are highly conserved and form a complex involved in divisome assembly and regulation. They are likely part of the core machinery as well. In this proposal, we will test our model for cooperative assembly of FtsZ, further exploit FtsE/FtsX to gain further insight into its role in divisome assembly and regulation. We will also take advantage of dominant negative mutations in essential cell genes that were isolated by a novel screen to understand the changes in protein conformation that lead to changes in protein interactions that regulate the divisome. We will also use the knowledge gained from studying cell division to construct a minimal divisome.
The process of cytokinesis is essential to cellular life, and as such merits study. By continuing to unravel the mechanism of cytokinesis and the regulatory features used by the cell to control this process, it is anticipated that novel targets for the antibiotics will continue to emerge.
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