Allosteric transcriptional regulation via changes in the overall topology of the core promoter
Abstract
Many transcriptional activators act at a distance from core promoter elements and work by recruiting RNA polymerase through protein-protein interactions. We show here how the prokaryotic regulatory protein CueR both represses and activates transcription by differentially modulating local DNA structure within the promoter. Structural studies reveal that the repressor state slightly bends the promoter DNA, precluding optimal RNA polymerase-promoter recognition. Upon binding a metal ion in the allosteric site, CueR switches into an activator conformation. It maintains all protein-DNA contacts but introduces torsional stresses that kink and undertwist the promoter, stabilizing an A-DNA-like conformation. Finally, these factors switch on and off transcription by exerting dynamic control of DNA stereochemistry, reshaping the core promoter and making it a better or worse substrate for polymerase.
- Authors:
-
- Northwestern Univ., Evanston, IL (United States)
- Publication Date:
- Research Org.:
- Northwestern Univ., Evanston, IL (United States)
- Sponsoring Org.:
- USDOE
- OSTI Identifier:
- 1345045
- Grant/Contract Number:
- AC02-06CH11357
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Science
- Additional Journal Information:
- Journal Volume: 349; Journal Issue: 6250; Journal ID: ISSN 0036-8075
- Publisher:
- AAAS
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES
Citation Formats
Philips, Steven J., Canalizo-Hernandez, Monica, Yildirim, Ilyas, Schatz, George C., Mondragon, Alfonso, and O'Halloran, Thomas V. Allosteric transcriptional regulation via changes in the overall topology of the core promoter. United States: N. p., 2015.
Web. doi:10.1126/science.aaa9809.
Philips, Steven J., Canalizo-Hernandez, Monica, Yildirim, Ilyas, Schatz, George C., Mondragon, Alfonso, & O'Halloran, Thomas V. Allosteric transcriptional regulation via changes in the overall topology of the core promoter. United States. https://doi.org/10.1126/science.aaa9809
Philips, Steven J., Canalizo-Hernandez, Monica, Yildirim, Ilyas, Schatz, George C., Mondragon, Alfonso, and O'Halloran, Thomas V. Fri .
"Allosteric transcriptional regulation via changes in the overall topology of the core promoter". United States. https://doi.org/10.1126/science.aaa9809. https://www.osti.gov/servlets/purl/1345045.
@article{osti_1345045,
title = {Allosteric transcriptional regulation via changes in the overall topology of the core promoter},
author = {Philips, Steven J. and Canalizo-Hernandez, Monica and Yildirim, Ilyas and Schatz, George C. and Mondragon, Alfonso and O'Halloran, Thomas V.},
abstractNote = {Many transcriptional activators act at a distance from core promoter elements and work by recruiting RNA polymerase through protein-protein interactions. We show here how the prokaryotic regulatory protein CueR both represses and activates transcription by differentially modulating local DNA structure within the promoter. Structural studies reveal that the repressor state slightly bends the promoter DNA, precluding optimal RNA polymerase-promoter recognition. Upon binding a metal ion in the allosteric site, CueR switches into an activator conformation. It maintains all protein-DNA contacts but introduces torsional stresses that kink and undertwist the promoter, stabilizing an A-DNA-like conformation. Finally, these factors switch on and off transcription by exerting dynamic control of DNA stereochemistry, reshaping the core promoter and making it a better or worse substrate for polymerase.},
doi = {10.1126/science.aaa9809},
journal = {Science},
number = 6250,
volume = 349,
place = {United States},
year = {Fri Aug 21 00:00:00 EDT 2015},
month = {Fri Aug 21 00:00:00 EDT 2015}
}
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