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

Research output: Contribution to journalArticle

45 Citations (Scopus)

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
Pages (from-to)877-881
Number of pages5
JournalScience
Volume349
Issue number6250
DOIs
Publication statusPublished - Aug 21 2015

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Allosteric Regulation
DNA
DNA-Directed RNA Polymerases
Proteins
A-Form DNA
Allosteric Site
Nucleic Acid Conformation
Metals
Ions

ASJC Scopus subject areas

  • General
  • Medicine(all)

Cite this

Philips, S. J., Canalizo-Hernandez, M., Yildirim, I., Schatz, G. C., Mondragón, A., & O'Halloran, T. V. (2015). Allosteric transcriptional regulation via changes in the overall topology of the core promoter. Science, 349(6250), 877-881. https://doi.org/10.1126/science.aaa9809

Allosteric transcriptional regulation via changes in the overall topology of the core promoter. / Philips, Steven J.; Canalizo-Hernandez, Monica; Yildirim, Ilyas; Schatz, George C; Mondragón, Alfonso; O'Halloran, Thomas V.

In: Science, Vol. 349, No. 6250, 21.08.2015, p. 877-881.

Research output: Contribution to journalArticle

Philips, SJ, Canalizo-Hernandez, M, Yildirim, I, Schatz, GC, Mondragón, A & O'Halloran, TV 2015, 'Allosteric transcriptional regulation via changes in the overall topology of the core promoter', Science, vol. 349, no. 6250, pp. 877-881. https://doi.org/10.1126/science.aaa9809
Philips SJ, Canalizo-Hernandez M, Yildirim I, Schatz GC, Mondragón A, O'Halloran TV. Allosteric transcriptional regulation via changes in the overall topology of the core promoter. Science. 2015 Aug 21;349(6250):877-881. https://doi.org/10.1126/science.aaa9809
Philips, Steven J. ; Canalizo-Hernandez, Monica ; Yildirim, Ilyas ; Schatz, George C ; Mondragón, Alfonso ; O'Halloran, Thomas V. / Allosteric transcriptional regulation via changes in the overall topology of the core promoter. In: Science. 2015 ; Vol. 349, No. 6250. pp. 877-881.
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