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Prof. Tung Le, Centre for Microbial Interactions, Norwich: The silence of the genes: How a molecular clamp shuts down long-range gene expression in multi-drug resistance plasmids?

Speaker Series. Long-range gene regulation in bacteria is rare and typically attributed to DNA looping and supercoiling. In this study, we use a combination of biophysical approaches—including X-ray crystallography and single-molecule analysis—to investigate the KorB–KorA system in Escherichia coli. Our findings reveal that long-range gene silencing on the plasmid RK2, a key driver of multi-drug resistance in diverse Gram-negative bacteria, is facilitated cooperatively by the DNA-sliding clamp KorB and the clamp-locking protein KorA. We demonstrate that KorB functions as a CTPase clamp capable of entrapping and sliding along DNA to reach target promoters up to 1.5 kb away. By resolving the tripartite crystal structure of the KorB–KorA–DNA complex, we show that KorA locks KorB into a closed clamp state. When bound to DNA, KorA enhances repression by halting KorB’s sliding at target promoters, thereby blocking RNA polymerase holoenzyme access. Overall, our study elucidates the molecular mechanism underlying KorB’s dual role as a DNA-sliding clamp and a co-repressor, offering an alternative model for long-range gene regulation in bacteria. In the final part of my talk, I will discuss the evolutionary adaptation of CTPase enzymes to perform a wide range of biological functions.

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