Department of Physiology Seminar Series Joachim Weber, Ph.D. Assistant Professor Texas Tech University Department of Chemistry & Biochemistry Room ACB240, 3:30-4:30 p.m., Tuesday, June 12, 2007 “ATP Synthase – The World’s Smallest Rotary Motor” ATP is the fuel for energy-requiring processes in all organisms. Every day the human body produces approximately its own weight in ATP. The enzyme ATP synthase is responsible for the bulk of ATP synthesis. It uses a transmembrane proton gradient to synthesize ATP from ADP and inorganic phosphate, and it hydrolyses ATP to transport protons across the membrane. ATP synthesis/ hydrolysis and proton translocation are tightly coupled by a unique mechanism, subunit rotation, making ATP synthase a very efficient rotary nanomotor. The long-term goal of Dr. Weber’s research is to understand the mechanism of ATP synthase in molecular detail. Working with Dr. Alan Senior (University of Rochester, NY), Dr. Weber developed fluorescence-based assays for protein-ligand and protein-protein interactions in ATP synthase. Tryptophan residues in the three catalytic nucleotide binding sites were used as probes to monitor site occupancy by ATP and ADP, leading to a model for the mechanism of ATP synthase. Tryptophan fluorescence and site-directed mutagenesis were applied to investigate the contacts between subunits that hold the enzyme together during subunit rotation. Currently, Dr. Weber’s work focuses on the question how ATP binding and hydrolysis in the catalytic site drive subunit rotation, using a variety of approaches. The applied techniques range from molecular biology (site-directed mutagenesis) to biochemistry (protein chemistry, enzyme kinetics) to biophysical chemistry (fluorescence spectroscopy). Molecular dynamics simulations and torque measurements by single-molecule analysis are performed in collaboration with other laboratories. Recent Publications “Structural characterization of the interaction of the d and a subunits of the Escherichia coli F1F0-ATP synthase by NMR spectroscopy”, Wilkens, S.; Borchardt, D.; Weber, J.; Senior, A.E. Biochemistry 2005, 44, 11786–11794. "Happy Motoring with ATP Synthase", Senior, A.E.; Weber, J. Nature Struct. Mol. Biol. 2004, 11, 110-112. “Fluorescent Probes Applied to Catalytic Cooperativity in ATP Synthase”, Weber, J.; Senior, A. E. Methods Enzymol. 2004, 380, 132-152. Persons with disabilities who may need auxiliary aids or services are requested to contact Josie Martinez at least 24 hours prior to this seminar so that appropriate arrangements can be made. Department of Physiology: Josie Martinez STOP 6551 | 806-743-2521