Other School of Medicine Affiliations
Institute for Medicine and Engineering
Pennsylvania Muscle Institute
Cell and Molecular Biology Graduate Program
Program in Cellular Physiology
Bioengineering Program
Biophysics Program

Degrees
B.S., Northwestern University, 1968
M.D., Ph.D., University of Pennsylvania, 1975

Honors
Upjohn Achievement Award, University of Pennsylvania
Trainee, Medical Scientist Training Program, University of Pennsylvania
Research Fellowship, Muscular Dystrophy Association
National Research Service Award, (NIH)
Research Career Development 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
Distinguished Speaker for Graduate Student Research Forum, University of Cincinnati

Professional Affiliations
American Physiological Society
Society of General Physiologists
Physiological Society, U.K.
Physiological Society of Philadelphia
Biophysical Society

Research Interests
Molecular mechanism of muscle contraction, mechanochemistry and structural biology

Research Description
Motor Proteins
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.We are relating the structural changes to the enzymatic reactions and mechanical steps of the energy transduction mechanism

Ribosomal Elongation Factors
Although the ribosome has been studied extensively since the unraveling of the genetic code, how it accomplishes the enormous fidelity of translating messenger RNA codons 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.

Representative Publications
Cheung A, Dantzig JA, Hollingworth S, Baylor SM, Goldman YE, Mitchison TJ, Straight AF. A small-molecule inhibitor of skeletal muscle myosin II. Nat. Cell. Biol., 4:83-8. 2002.

Hopkins SC, Sabido-David C, van der Heide UA, Ferguson RE, Brandmeier BD, Dale RE, Kendrick-Jones J, Corrie JE, Trentham DR, Irving M, Goldman YE. Orientation changes of the myosin light chain domain during filament sliding in active and rigor muscle. J. Mol. Biol., 318:1275-91. 2002.

Bell MG, Dale RE, van der Heide UA, Goldman YE. Polarized fluorescence depletion reports orientation distribution and rotational dynamics of muscle cross-bridges. Biophys. J., 83:1050-73. 2002.

Forkey JN, Quinlan ME, Alexander Shaw M, Corrie JE, Goldman YE. Three-dimensional structural dynamics of myosin V by single-molecule fluorescence polarization. Nature, 422:399-404. 2003.

Shaw MA, Ostap EM, Goldman YE. Mechanism of inhibition of skeletal muscle actomyosin by N-Benzyl-p-toluenesulfonamide. Biochemistry. 42:6128-35. 2003.

Yildiz A, Forkey JN, McKinney SA, Ha T, Goldman YE, Selvin PR. Myosin V walks hand-over-hand: single fluorophore imaging with 1.5-nm localization. Science, 300:2061-5. 2003.

Click here for a full list of publications
(searches the National Library of Medicine's PubMed database.)