Sherwin S. Lehrer, Ph.D.

Sherwin S. Lehrer, Ph.D.

Senior Scientist
Skeletal nemaline myopathy, cardiac hypertrophic myopathy, heart disease
lehrer@bbri.org


Research Summary

The long-range goal of the research in my lab is to understand the mechanism of tropomyosin action at the molecular level in conjunction with the other important components of the regulatory system,  actin, myosin, troponin (striated muscle) and caldesmon (smooth muscle). To achieve this goal we study the molecular and regulatory properties of recombinant and native Tms. The research design and techniques used to achieve these aims include:  effects of Tm on actomyosin ATPase activity;  studies of changes in proximity and dynamics of thin filament components using fluorescence and crosslinking probes; stopped-flow kinetic measurements to learn about the rates of transitions between the regulatory states; studies of the localization of labeled proteins incorporated into myofibrils using fluorescence microscopy imaging.

 

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Selected Publications

  • Sumida, J. P., Wu, E. & Lehrer, S. S. (2008). Conserved Asp-137 imparts flexibility to tropomyosin and affects function. J Biol Chem 283, 6728-34.
  • Coulton, A. T., Koka, K., Lehrer, S. S. & Geeves, M. A. (2008). Role of the head-to-tail overlap region in smooth and skeletal muscle beta-tropomyosin. Biochemistry 47, 388-97.
  • Coulton, A., Lehrer, S. S. & Geeves, M. A. (2006). Functional homodimers and heterodimers of recombinant smooth muscle tropomyosin. Biochemistry 45, 12853-8.
  • Bacchiocchi, C., Graceffa, P., and Lehrer, S. S. (2004) Myosin-induced  movement of  aa,  ab, and  bb smooth muscle tropomyosin on actin observed by multisite FRET.  Biophys J. 86, 2295-2307.
  • Maytum, R., Geeves, M. A. & Lehrer, S. S., (2002) A Modulatory Role for the Troponin T Tail domain in Thin Filament Regulation, J. Biol. Chem, 277, 29774-29780.
  • Bacchiocchi, C., & Lehrer, S. S., (2002) Ca2+-induced Movement of Tropomyosin in skeletal Muscle Thin Filaments observed by Multi-site FRET, Biophys. J., 82, 1524-1536.
  • Geeves, M.A., Chai, M. & Lehrer, S.S. (2000). Inhibition of actin-myosin subfragment 1 ATPase activity by troponin I and IC: Relationship 5to the thin filament states of muscle. Biochemistry 39, 9345-9350.
  • Lehrer, S.S. & M.A. Geeves (1998) The muscle thin filament as a classical cooperative/allosteric regulatory system.  J. Mol. Biol. 277, 1081-1089.

 

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

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