Yale E. Goldman

Professor

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215-898-4017
goldmany@pennmedicine.upenn.edu

615B Clinical Research Building

415 Curie Boulevard

Philadelphia, PA 19104

Research Description

Molecular Motors:

Motor proteins and GTP-binding proteins (G-proteins) share many structural and functional attributes. Molecular motors myosin, dynein and kinesin are prototype biological energy transducers that can be understood at a particularly fine level of detail. The obvious functional output (force and motion) allow the reaction sequence to be probed by single molecule biophysical, 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 nanometer tracking of single fluorescent molecules, bifunctional fluorescent probes and infrared optical traps (laser tweezers) to map the real-time domain motions of the motor proteins.

Protein Synthesis:

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 is the motor catalyzing translocation of tRNAs and mRNA. 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.

Biophysical Instrumentation:

Technology development spurs research by enabling new types of measurements. We have developed several new methods including “caged” molecules for rapid reaction kinetics in organized biophysical systems, oxygen exchange, polarized total internal fluorescence microscopy for structural dynamics, ultra-high speed optical traps, “parallax view” 3D tracking, alternating laser excitation (ALEX) microscopy for single molecule FRET measurements and others.

Diversity & Inclusion Initiatives

  • Member, Committee on the Sciences and the Arts of the Franklin Institute
Degrees & Education

BS, Northwestern University, 1968

MD, PhD, University of Pennsylvania, 1975

Honors & Awards

Upjohn Achievement Award, University of Pennsylvania

Trainee, Medical Scientist Training Program, University of Pennsylvania

National Research Service Award, (NIH)

Bowditch Lecturer of the American Physiological Society

Lindback Foundation Award for Distinguished Teaching

Lamport Lecturer of the University of Washington, School of Medicine

Stanley N. Cohen School of Medicine Biomedical Research Award

President of the Biophysical Society

Fellow of the Biophysical Society

Fellow of the American Association for the Advancement of Science

Biophysical Society Distinguished Service Award

Biophysical Society Kazu Kinosita Single Molecule Biophysics Award

Member, National Academy of Sciences

Other Perelman School of Medicine Affiliations

Institute for Medicine and Engineering

Pennsylvania Muscle Institute

Department of Biochemistry and Molecular Biophysics

Department of Mechanical Engineering and Applied Mechanics

Cell and Molecular Biology Graduate Program

Program in Cellular Physiology

Bioengineering Program

Biophysics Program

Professional Affiliations

American Physiological Society

Society of General Physiologists

Biophysical Society

Recent Publications
June 22, 2020
The mechanochemistry of the kinesin-2 KIF3AC heterodimer is related to strain-dependent kinetic properties of KIF3A and KIF3C
Yale E. Goldman, MD, PhD
Bensel BM, Woody MS, Pyrpassopoulos S, Goldman YE, Gilbert SP, Ostap EM - DOI: 10.1073/pnas.1916343117 - PMID: 32571914
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February 19, 2021
Myosin with hypertrophic cardiac mutation R712L has a decreased working stroke which is rescued by omecamtiv mecarbil
Yale E. Goldman, MD, PhD
Snoberger A, Barua B, Atherton JL, Shuman H, Forgacs E, Goldman YE, Winkelmann DA, Ostap EM - DOI: 10.7554/eLife.63691 - PMID: 33605878
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February 24, 2021
No hype in hyperspace
Yale E. Goldman, MD, PhD
DOI: 10.1016/j.bpj.2021.02.026 - PMID: 33711256
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