Allosteric transcriptional regulation via changes in the overall topology of the core promoter

Steven J. Philips, Monica Canalizo-Hernandez, Ilyas Yildirim, George C. Schatz, Alfonso Mondragón*, Thomas V. O'Halloran

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

60 Scopus citations

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-form DNA - like conformation. 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.

Original languageEnglish (US)
Pages (from-to)877-881
Number of pages5
JournalScience
Volume349
Issue number6250
DOIs
StatePublished - Aug 21 2015

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'Allosteric transcriptional regulation via changes in the overall topology of the core promoter'. Together they form a unique fingerprint.

Cite this