Yale E. Goldman
Professor, Dept of Physiology
Director, Pennsylvania Muscle Institute

Cell Biology and Physiology Program

Address

D700 Richards Building
3700 Hamilton Walk
Philadelphia, PA 19104

Office tel.: 215 898-4017
Lab tel.: 215 898-4247
Fax: 215 898-2653
E-mail: goldmany@mail.med.upenn.edu

Link(s)

Pennsylvania Muscle Institute (PMI)

Dr. Goldman's PMI Webpage

Education

Northwestern University, Illinois: BS (Electrical Engineering), 1969.

University of Pennsylvania, School of Medicine: PhD (Physiology), 1975.

University of Pennsylvania, School of Medicine: MD (Medicine), 1975.

University College, U.K.: Post-Doctoral Fellowship (Physiology), 1975-1979.

Research Interests

• Relating the structural changes to enzymatic reactions and mechanical steps of the energy transduction mechanism by mapping the real-time domain motions of the motor proteins and ribosomal elongation factors.

Key words: Actin, Molecular motor, Motility, Myosin, Structural dynamics, Fluorescence, Muscle, Ribosome, Protein synthesis, G-Protein, ATPase, Laser Photolysis, Caged ATP, Optical Trap.

Search PubMed for articles

Description of Research

Motor proteins and GTP-binding proteins (G-proteins) share many structural and functional attributes. Muscle is a prototype biological energy transducer that can be understood at a particularly fine level of detail. The nearly crystalline organization of actin and myosin within a fiber allows the reaction sequence to be probed by biophysical, physiological, chemical and structural studies. A cyclic interaction between actin and myosin transforms free energy of splitting ATP into motion and mechanical work. Modified forms of this mechanism power other cell biological motions such as targeted vesicle transport and cell division. We are using novel biophysical techniques, including laser photolysis of ‘caged molecules’, bifunctional fluorescent probes and single molecule fluorescence polarization to map the real-time domain motions of the motor proteins.

Although the ribosome has been studied extensively since the unraveling of the genetic code, how it accomplishes the enormous fidelity of messenger RNA translation into amino acid sequences during protein biosynthesis is not understood. The ribosome is a motor translocating along the mRNA exactly 3 bases per elongation cycle. Energy from splitting GTP by G-protein elongation factors (EFs) is transformed into translational accuracy and maintenance of the reading frame. Codon-anticodon base pairing between mRNA and tRNA ‘reads’ the code, but EF-Tu ‘proofreads’ it. EF-G may be the motor. Powerful techniques developed for studies on motor proteins, including single molecule fluorescence and optical traps, may be applied to understand the structural biology, energetics and function of EFs in their working environment.

Recent Publications

Goldman, Y.E. and Homsher, E. Molecular Physiology of the Cross-Bridge Cycle. In: Myology, 3rd Ed. A. G. Engel, C. Franzini-Armstrong (eds). McGraw-Hill Medical Publishing Division, New York. pp. 187-202. 2004.

Liu, J., Reedy, M.C., Goldman, Y.E., Franzini-Armstrong, C., Sasaki, H., Tregear, R.T., Lucaveche, C., Winkler, H., Baumann, B.A.J., Squire, J.M., Irving, T.C., Reedy, M.K., and Taylor, K.A. Electron Tomography of Fast Frozen, Stretched Rigor Fibers Reveals Elastic Distortions in the Myosin Crossbridges. J. Struct. Biol., 147:247-258. 2004.

Forkey, J.N., Quinlan, M.E., and Goldman, Y.E. Measurement of Single Macromolecule Orientation by Total Internal Reflection Fluorescence Polarization Microscopy. Biophys. J. 2005. In Press.

Quinlan, M.E., Forkey, J.N., and Goldman, Y.E. Orientation of the Myosin Light Chain Region by Single and Multiple Molecule Total Internal Reflection Fluorescence Polarization Microscopy. Biophys. J. 2005. In Press.

Vanzi, F., Takagi, Y., Shuman, H., 32-Cooperman, B.S., and Goldman, Y.E. Mechanical Studies of Single Ribosome/mRNA Complexes. Biophys. J. 2005. In Press.

Lab

Rotation Projects for 2006-2007

• Unconventional Myosins
• Dynein/Myosin Interactions
• Protein Synthesis
• Ribosomal Elongation Factors

Lab personnel:

Dr. Jody Dantzig-Brody, Research Faculty
Rama Kudaravalli, Research Technician
JoAnn Rodgers, Administrative Coordinator
Huy Pham, Research Technician
Graham Dempsey, Research Technician
Jennifer Petrina, Business Administrator
Jennifer Ross, Research Faculty
Yuhong Wang, Research Faculty
Yujie Sun, Research Faculty
Joby Geevarghese, Electrical Engineer