Joachim Weber

Assistant Professor

 

PhD, Medical University of Lübeck, Germany, 1990

Postdoctoral, University of Rochester, NY, 1990-1995

Research Assistant Professor, University of Rochester, NY, 1995-2003

 

Awards
Annual Prize of the Faculty for Science of the Medical University of Lübeck, Germany, 1990

Postdoctoral Research Grant from the German Research Society (DFG), 1990-1991

National Institutes of Health, 2004-2009

 

   

 

Phone: (806) 742-1297

Fax: (806) 742-1289

 

 

Biochemistry

 

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.

 

 Selected 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.

  • "Quantitative Determination of Direct Binding of b Subunit to F1 in Escherichia coli F1F0-ATP Synthase", Weber, J.; Wilke-Mounts, S.; Nadanaciva, S.; Senior, A.E. J. Biol. Chem. 2004, 279, 11253-11258.

  • "F1F0-ATP Synthase: Analysis of Sequence Determinants in the N-terminal Region of α Subunit for Binding of δ Subunit",  Weber, J.; Muharemagic, A.; Wilke-Mounts, S.; Senior, A.E. J. Biol. Chem. 2004, 279, 25673-25679.

  • "ATP Synthesis Driven by Proton Transport in ATP Synthase”, Weber, J.; Senior, A.E..  FEBS Lett. 2003, 545, 61-70.

  • "Identification of the F1-binding Surface on the δ-subunit of ATP Synthase”, Weber, J.; Wilke-Mounts, S.; Senior, A.E. J. Biol. Chem. 2003, 278, 13409-13416.

  • "F1F0-ATP Synthase: Binding of δ Subunit to a 22-residue Peptide Mimicking the N-terminal Region of α Subunit”, Weber, J.; Muharemagic, A.; Wilke-Mounts, S.; Senior, A.E. J. Biol. Chem. 2003, 278, 13623-13626.

  • "Cysteine-reactive Fluorescence Probes of Catalytic Sites of ATP Synthase", Weber, J.; Bijol, V.; Wilke-Mounts, S.; Senior, A.E. Arch. Biochem. Biophys. 2002, 397, 1-10.

  • "The Molecular Mechanism of ATP Synthesis by F1F0-ATP Synthase", Senior, A.E.; Nadanaciva, S.; Weber, J. Biochim. Biophys. Acta 2002, 1553, 188-211.

  • "Quantitative Determination of Binding Affinity of  δ Subunit in Escherichia coli F1-ATPase.  Effect of Mutation, Mg2+, and pH on Kd”, Weber, J.; Wilke-Mounts, S.; Senior, A.E.. J. Biol. Chem. 2002, 277, 18390-18396.

  • "Bi-site Catalysis in F1-ATPase: Does it Exist?", Weber, J.; Senior, A.E. J. Biol. Chem. 2001, 276, 35422-35428.

  • "ATP Synthase: What We Know About ATP Hydrolysis and What We Do Not Know About ATP Synthesis", Weber, J.; Senior, A.E. Biochim. Biophys. Acta 2000, 1458, 300-309.

  • "Features of F1-ATPase Catalytic and Noncatalytic Sites Revealed by Fluorescence Lifetimes and Acrylamide Quenching of Specifically-inserted Tryptophan Residues",  Weber, J.; Senior, A.E. Biochemistry 2000, 39, 5287-5294.

  • "ATP-driven Rotation of the Gamma Subunit in F1-ATPase", Weber, J.; Nadanaciva, S.; Senior, A.E. FEBS Lett. 2000, 483, 1-5.

 

 

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