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The myosin converter domain modulates muscle performance

Nature Cell Biology volume 4, pages 312–317 (2002)Cite this article

Abstract

Myosin is the molecular motor that powers muscle contraction as a result of conformational changes during its mechanochemical cycle. We demonstrate that the converter, a compact structural domain that differs in sequence between Drosophila melanogaster myosin isoforms, dramatically influences the kinetic properties of myosin and muscle fibres. Transgenic replacement of the converter in the fast indirect flight muscle with the converter from an embryonic muscle slowed muscle kinetics, forcing a compensatory reduction in wing beat frequency to sustain flight. Conversely, replacing the embryonic converter with the flight muscle converter sped up muscle kinetics and increased maximum power twofold, compared to flight muscles expressing the embryonic myosin isoform. The substitutions also dramatically influenced in vitro actin sliding velocity, suggesting that the converter modulates a rate-limiting step preceding cross-bridge detachment. Our integrative analysis demonstrates that isoform-specific differences in the myosin converter allow different muscle types to meet their specific locomotion demands.

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Figure 1: The location of alternative domains in Drosophila myosin and expression patterns of alternative converters.
Figure 2: Longitudinal and transverse sections of transgenic muscle fibres viewed by electron microscopy.
Figure 3: Flight muscle mechanical properties influenced by the converter.

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Acknowledgements

We thank R. Milligan for the myosin S1 structure shown in Fig. 1, D. Warshaw, S. Lowey, K. Trybus, J. Moore and K. Littlefield for helpful discussions, and W. Barnes, W. Kronert and G. Manipon for technical assistance. We also appreciate the valuable suggestions of an anonymous reviewer. This work was supported by research grants from the National Institutes of Health (NIH) to S.I.B. (GM 32443) and D.W.M., by NIH Minority Biomedical Research Support fund (GM 58906) to F.S. and by postdoctoral fellowships to D.M.S. from the NIH and the American Heart Association, Western States Affiliate.

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Authors and Affiliations

  1. Department of Biology, Molecular Biology Institute, and the Heart Institute, San Diego State University, San Diego, 92182–4614, California, USA

    Douglas M. Swank, Jennifer A. Suggs, Floyd Sarsoza, Annie Lee & Sanford I. Bernstein

  2. Department of Chemistry, San Diego State University, San Diego, 92182-1030, California, USA

    Aileen F. Knowles

  3. Department of Molecular Physiology and Biophysics, University of Vermont, Burlington, 05405, Vermont, USA

    David W. Maughan

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  1. Douglas M. Swank
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Correspondence to Douglas M. Swank.

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Swank, D., Knowles, A., Suggs, J. et al. The myosin converter domain modulates muscle performance. Nat Cell Biol 4, 312–317 (2002). https://doi.org/10.1038/ncb776

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