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Alteration in crossbridge kinetics caused by mutations in actin

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Abstract

THE generation of force during muscle contraction results from the interaction of myosin and actin. The kinetics of this force generation vary between different muscle types and within the same muscle type in different species1-2. Most attention has focused on the role of myosin isoforms in determining these differences3-5. The role of actin isoforms has received little attention, largely because of the lack of a suitable cell type in which the myosin isoform remains constant yet the actin isoforms vary. An alternative approach would be to examine the effect of actin mutations, however, most of these cause such gross disruption of muscle structure that mechanical measurements are impossible6-10. We have now identified two actin mutations which, despite involving conserved amino acids, can assemble into virtually normal myofibrils11. These amino-acid changes in actin significantly affect the kinetics of force generation by muscle fibres. One of the mutations is not in the putative myosin-binding site, demonstrating the importance of long-range effects of amino acids on actin function.

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Authors and Affiliations

  1. Department of Biology, University of York, York, Y01 5DD, UK

    Douglas R. Drummond, Michelle Peckham, John C. Sparrow & David C. S. White

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  1. Douglas R. Drummond
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  2. Michelle Peckham
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  3. John C. Sparrow
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  4. David C. S. White
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Drummond, D., Peckham, M., Sparrow, J. et al. Alteration in crossbridge kinetics caused by mutations in actin. Nature 348, 440–442 (1990). https://doi.org/10.1038/348440a0

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