CTP switches in bacterial chromosome segregation and physiology: structures, functions, and mechanisms

ATP and GTP switches are extensively used to control conformations and functions of proteins in a wide range of biological processes. However, CTP switches have rarely been found in biology.

Recent work from our laboratory and others has shown that ParB is a founding member of a CTPase protein family that uses a CTP switch to regulate bacterial chromosome segregation. We hypothesize that CTP switches are currently unappreciated and may be widespread.

In the proposed work we will exploit the tripartite ParABS system from Caulobacter crescentus to elucidate the structure, function, and mechanism of the CTP switch that ensures faithful chromosome segregation.

Next, we will investigate how other CTP switches regulate membrane association and gene expression by employing Noc and KorB (proteins crucial for chromosome integrity and plasmid transmission, respectively) as models.

Lastly, we will identify and characterize other CTP switch proteins in C.crescentus and systematically discover putative CTP-binding/CTPase proteins across all sequenced bacterial genomes.

Altogether, this work will provide fundamental knowledge on the mechanism and evolution of CTP switches and open new and unexpected horizons in numerous fields beyond bacterial chromosome segregation.

Moreover, our immediate research on plasmid/chromosome segregation and transmission may inform strategies to combat plasmid-borne antibiotic resistance.