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Publication Abstract from PubMed

Examples of long-range gene regulation in bacteria are rare and generally thought to involve DNA looping. Here, using a combination of biophysical approaches including X-ray crystallography and single-molecule analysis for the KorB-KorA system in Escherichia coli, we show that long-range gene silencing on the plasmid RK2, a source of multi-drug resistance across diverse Gram-negative bacteria, is achieved cooperatively by a DNA-sliding clamp, KorB, and a clamp-locking protein, KorA. We show that KorB is a CTPase clamp that can entrap and slide along DNA to reach distal target promoters up to 1.5 kb away. We resolved the tripartite crystal structure of a KorB-KorA-DNA co-complex, revealing that KorA latches KorB into a closed clamp state. DNA-bound KorA thus stimulates repression by stalling KorB sliding at target promoters to occlude RNA polymerase holoenzymes. Together, our findings explain the mechanistic basis for KorB role switching from a DNA-sliding clamp to a co-repressor and provide an alternative mechanism for long-range regulation of gene expression in bacteria.

KorB switching from DNA-sliding clamp to repressor mediates long-range gene silencing in a multi-drug resistance plasmid.,McLean TC, Balaguer-Perez F, Chandanani J, Thomas CM, Aicart-Ramos C, Burick S, Olinares PDB, Gobbato G, Mundy JEA, Chait BT, Lawson DM, Darst SA, Campbell EA, Moreno-Herrero F, Le TBK Nat Microbiol. 2025 Feb;10(2):448-467. doi: 10.1038/s41564-024-01915-3. Epub 2025 , Jan 23. PMID:39849085^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.