CueR activates transcription through a DNA distortion mechanism
- 31 December 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Chemical Biology
- Vol. 17 (1), 57-64
- https://doi.org/10.1038/s41589-020-00653-x
Abstract
The MerR-family transcription factors (TFs) are a large group of bacterial proteins responding to cellular metal ions and multiple antibiotics by binding within central RNA polymerase-binding regions of a promoter. While most TFs alter transcription through protein-protein interactions, MerR TFs are capable of reshaping promoter DNA. To address the question of which mechanism prevails, we determined two cryo-EM structures of transcription activation complexes (TAC) comprisingEscherichia coliCueR (a prototype MerR TF), RNAP holoenzyme and promoter DNA. The structures reveal that this TF promotes productive promoter-polymerase association without canonical protein-protein contacts seen between other activator proteins and RNAP. Instead, CueR realigns the key promoter elements in the transcription activation complex by clamp-like protein-DNA interactions: these induce four distinct kinks that ultimately position the -10 element for formation of the transcription bubble. These structural and biochemical results provide strong support for the DNA distortion paradigm of allosteric transcriptional control by MerR TFs.Keywords
Funding Information
- Ministry of Science and Technology of the People’s Republic of China (2018YFA0507800, 2018YFA0900701)
- National Natural Science Foundation of China (31970040, 31822001)
- Foundation for the National Institutes of Health (GM038784-29, CA193419)
- Chinese Academy of Sciences (QYZDB-SSW-SMC005)
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