title: TRANSCRIPTION. 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-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.
authors: Department of Molecular Biosciences, Northwestern University, Evanston, IL 60208, USA.
authors: Steven J
authors: SJ
authors: Philips
authors: Department of Chemistry, Northwestern University, Evanston, IL 60208, USA.
authors: Monica
authors: M
authors: Canalizo-Hernandez
authors: Department of Chemistry, Northwestern University, Evanston, IL 60208, USA.
authors: Ilyas
authors: I
authors: Yildirim
authors: Department of Chemistry, Northwestern University, Evanston, IL 60208, USA.
authors: George C
authors: GC
authors: Schatz
authors: Department of Molecular Biosciences, Northwestern University, Evanston, IL 60208, USA. t-ohalloran@northwestern.edu a-mondragon@northwestern.edu.
authors: Alfonso
authors: A
authors: Mondragón
authors: Department of Molecular Biosciences, Northwestern University, Evanston, IL 60208, USA. Department of Chemistry, Northwestern University, Evanston, IL 60208, USA. The Chemistry of Life Processes Institute, Northwestern University, Evanston, IL 60208, USA. t-ohalloran@northwestern.edu a-mondragon@northwestern.edu.
authors: Thomas V
authors: TV
authors: O'Halloran
mesh_terms: D000494:Allosteric Regulation; D000495:Allosteric Site; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism*; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D012321:DNA-Directed RNA Polymerases / Q000378:metabolism; D009690:Nucleic Acid Conformation; D011401:Promoter Regions, Genetic / Q000235:genetics*; D055503:Protein Multimerization; D017433:Protein Structure, Secondary; D014158:Transcription, Genetic; D015533:Transcriptional Activation
chemical_list: D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; C051124:MerR protein, Bacteria; D004247:DNA; D012321:DNA-Directed RNA Polymerases