Professor Tracy Nixon
Department of Biochemistry and Molecular Biology
The Pennsylvania State University
University Park, PA

Monday, March 29, 2010
10:00 am (CT)
3269 Beckman Institute

Abstract

AAA+ ATPases deliver mechanical work via conformational changes guided by nucleotide binding and hydrolysis, and evidence supports random, sequential or concerted mechanisms within the context of ring architectures. Detailed knowledge is lacking for the NtrC subclass of ATPase. These proteins regulate transcription to control virulence and other developmental activities in bacteria. We report a crystal structure and phenotypes for variants of NtrC1 of /Aquifex aeolicus. /Together they reveal how ATP binding at a subunit interface engages its arginine-finger. By altering the trajectory of an adjacent helix the interaction promotes a 10°-15° rigid body roll, primarily in the R-finger engaged protomer but also, and by distinct interactions, in both neighboring subunits. The roll extends the GAFTGA loop above the plane of the ring where it can bind to sigma-54. Hydrolysis and release of phosphate disengage the R-finger, triggering return rigid body roll – this pulls the GAFTGA loop down into the ring, providing force to remodel the sigma factor so that it can melt the promoter. The new insight about bi-directional impact of ATP binding sets the stage for learning how nucleotide binding and hydrolysis are distributed about the ring to control gene expression and development by regulating the s54-form of bacterial RNA polymerase.

2:30 pm: Coffee hour Theoretical and Computational Biophysics Group area, 3rd Floor Beckman