Yale E. Goldman, MD, PhD

faculty photo
Professor of Physiology
Department: Physiology

Contact information
Room D700 Richards Building
3700 Hamilton Walk
Philadelphia, PA 19104-6083
Office: (215) 898-4017
Fax: (215) 898-2653
Education:
B.S. (Electrical Engineering)
Northwestern University, 1969.
M.D. (Medicine)
University of Pennsylvania School of Medicine, 1975.
Ph.D. (Physiology)
University of Pennsylvania School of Medicine, 1975.
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Description of Research Expertise

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.

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.

Rotation Projects
- 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

Selected Publications

Yildiz, A., Forkey, J.N., McKinney, S.A., Ha, T., Goldman, Y.E., and Selvin, P.R.: Myosin V Walks Hand-over-hand: Single Fluorophore Imaging with 1.5-nm Localization. Science 300: 2062-2065, 2003.

Forkey, J.N., Quinlan, M.E., Shaw, M.A., Corrie, J.E., and Goldman, Y.E.: Three-dimensional Structural Dynamics of Myosin V by Single-molecule Fluorescence Polarization. Nature 422: 399-404, 2003.

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. Acc. Chem. Res. 38: 583-593, 2005.

Ross, J.L., Shuman, H., Holzbaur, E.L.F., and Goldman, Y.E.: Kinesin and Dynein-Dynactin at Intersecting Microtubules: Motor Number Affects Dynein but not Kinesin Function. Biophys. J. 92: 941a, 2007.

Sun, Y., Schroeder, H.W. 3rd, Beausang, JF, Homma, K, Ikebe, M, and Goldman, YE. : Myosin VI Walks "Wiggly" on Actin with Large and Variable Tilting. Mol Cell. 28: 954-964, 2007.

Arsenault, M.E., Zhao, H., Purohit, P.K., Goldman, Y.E., and Bau, H.H.. : Confinement and Manipulation of Actin Filaments by Electric Fields. Biophys J. 93: L42-L44, 2007.

Stapulionis R., Wang Y., Dempsey G.T., Khudaravalli R., Nielsen K.M., Cooperman B.S., Goldman Y.E., and Knudsen C.R.: Fast in vitro Translation System Immobilized on a Surface via Specific Biotinylation of the Ribosome. Biol Chem. 389: 1239-1249, 2008.

Dixit R., Ross J.L., and Goldman Y.E., and Holzbaur E.L. : Differential Regulation of Dynein and Kinesin Motor Proteins by Tau. Science 319: 1086-1089, 2008.

Beausang , J.F., Sun, Y., Quinlan, M.E., Forkey, J.N., and Goldman, Y.E. : Orientation and Rotational Motions of Single Molecules by Polarized Total Internal Reflection Fluorescence Microscopy. In: Single-Molecule Techniques. A Laboratory Manual. Eds. Selvin, P.R. and Ha, T. Cold Spring Harbor Press. Page: 507, 2008.

Dixit, R., Barnett, B., Lazarus, J.E., Tokito, M., Goldman, Y.E. and Holzbaur, E.L.F.: Microtubule Plus-End Tracking by CLIP-170 Requires EB1. , 106: 492-492. 2009. Proc. Nat. Acad. Sci. 106: 492-297, 2009.

Sun, Y., Dawicki McKenna, J., Murray, J.M., Ostap, E.M., and Goldman, Y.E. : Parallax: High Accuracy Three-Dimensional Single Molecule Tracking Using Split Images. Nano Lett. 7: 2676-2682, 2009.

Schroeder Harry W, Mitchell Chris, Shuman Henry, Holzbaur Erika L F, Goldman Yale E: Motor Number Controls Cargo Switching at Actin-Microtubule Intersections In Vitro. Current biology : CB Apr 2010.

Sun Yujie, Sato Osamu, Ruhnow Felix, Arsenault Mark E, Ikebe Mitsuo, Goldman Yale E: Single-molecule stepping and structural dynamics of myosin X. Nature structural & molecular biology 17(4): 485-91, Apr 2010.

Holzbaur Erika L F, Goldman Yale E: Coordination of molecular motors: from in vitro assays to intracellular dynamics. Current opinion in cell biology 22(1): 4-13, Feb 2010.

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Last updated: 03/18/2013
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