General transcription factor from Escherichia coli with a distinct mechanism of action

被引:3
作者
Vasilyev, Nikita [1 ]
Liu, Mengjie M. J. [1 ]
Epshtein, Vitaly [1 ]
Shamovsky, Ilya [1 ]
Nudler, Evgeny [1 ,2 ]
机构
[1] NYU, Sch Med, Dept Biochem & Mol Pharmacol, New York, NY 10016 USA
[2] NYU, Sch Med, Howard Hughes Med Inst, New York, NY 10016 USA
关键词
D O I
10.1038/s41594-023-01154-w
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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) sigma(70) holoenzyme. Structural and biochemical analysis of CedA bound to RNAP reveal that it bridges distant domains of beta and sigma(70) 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.
引用
收藏
页码:141 / 149
页数:21
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