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Crystal structure of the C-terminally truncated transcriptional repressor protein KorB from the RK2 plasmid complexed with CTP-gamma-SCrystal structure of the C-terminally truncated transcriptional repressor protein KorB from the RK2 plasmid complexed with CTP-gamma-S
Structural highlights
FunctionKORB2_ECOLX In conjunction with KorA, inhibits the transcription of the kilA, trfA and korAB operons. Is also involved in the negative control of the kilB operon. Publication Abstract from PubMedExamples 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. References
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