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Title: 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:
 [1];  [1];  [1];  [1];  [1];  [1]
  1. 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. doi: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. doi: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 = {2015},
month = {8}
}

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Cited by: 28 works
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