General transcription factor from Escherichia coli with a distinct mechanism of action.
General transcription factor from Escherichia coli with a distinct mechanism of action.
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DOI：
10.1038/s41594-023-01154-w
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发表时间：
2024-01
影响因子：
16.8
通讯作者：
Nudler, Evgeny
中科院分区：
文献类型：
--
作者：
Vasilyev, Nikita;Liu, Mengjie M. J.;Epshtein, Vitaly;Shamovsky, Ilya;Nudler, Evgeny
Gene expression in Escherichia coli is controlled by well-established mechanisms that activate or repress transcription. Here, we identify CedA as an unconventional transcription factor specifically associated with the RNA polymerase (RNAP) σ70 holoenzyme. Structural and biochemical analysis of CedA bound to RNAP reveal that it bridges distant domains of β and σ70 subunits to stabilize an open-promoter complex. CedA does so without contacting DNA. We further show that cedA is strongly induced in response to amino acid starvation, oxidative stress and aminoglycosides. CedA provides a basal level of tolerance to these clinically relevant antibiotics, as well as to rifampicin and peroxide. Finally, we show that CedA modulates transcription of hundreds of bacterial genes, which explains its pleotropic effect on cell physiology and pathogenesis. Here, using proteomics, next-generation sequencing, biochemistry and cryo-EM, the authors delineate the role of CedA as an unconventional transcription factor in Escherichia coli, which protects from different stressors, including antibiotics, by regulating the transcriptional landscape.
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