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A myosin II mutation uncouples ATPase activity from motility and shortens step size

Nature Cell Biology volume 3, pages 311–315 (2001)Cite this article

Abstract

It is thought that Switch II of myosin, kinesin and G proteins has an important function in relating nucleotide state to protein conformation. Here we examine a myosin mutant containing an S456L substitution in the Switch II region. In this protein, mechanical activity is uncoupled from the chemical energy of ATP hydrolysis so that its gliding velocity on actin filaments is only one-tenth of that of the wild type. The mutant spends longer in the strongly bound state and exhibits a shorter step size, which together account for the reduction in in vitro velocity. This is the first single point mutation in myosin that has been found to affect step size.

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Figure 1: The myosin ATPase cycle.
Figure 2: Crystal structure of Dictyostelium myosin II catalytic domain.
Figure 3: S456L myosin exhibits in vivo defects.
Figure 4: ATPase activity and motility of S456L myosin.
Figure 5: Measurement of step sizes.

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Acknowledgements

We thank A. Mehta for the wild type step size data and H. Warrick, D. Robinson and D. Hostetter for comments. C.T.M. was a Predoctoral Fellow of the Howard Hughes Medical Institute. R.S.R. is a Helen Hay Whitney Fellow.

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  1. Departments of Biochemistry and Developmental Biology, Stanford University School of Medicine, Stanford, 94305, California, USA

    Coleen T. Murphy, Ronald S. Rock & James A. Spudich

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  1. Coleen T. Murphy
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  2. Ronald S. Rock
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  3. James A. Spudich
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Correspondence to James A. Spudich.

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Murphy, C., Rock, R. & Spudich, J. A myosin II mutation uncouples ATPase activity from motility and shortens step size. Nat Cell Biol 3, 311–315 (2001). https://doi.org/10.1038/35060110

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