Research Highlights

Faculty in the Center for Structural Biology are highly active researchers who employ biophysical and biochemical approaches to study fundamental questions in structural biology. Some the topics being studied include:

  • Nucleic acid structure and function
  • Protein and RNA processing in the cell
  • Membrane protein structure and function
  • Mechanisms of macromolecular machines

Selected research projects by faculty in the Center are presented below.

Mondragón and O’Halloran Labs

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

Steven J. Philips, Monica Canalizo-Hernandez, Ilyas Yildrim, George C. Schatz, Alfonso Mondragón, and Thomas V. O’Halloran

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.