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A structural model for actin-induced nucleotide release in myosin

Nature Structural & Molecular Biology volume 10, pages 826–830 (2003)Cite this article

Abstract

Myosins are molecular motor proteins that harness the chemical energy stored in ATP to produce directed force along actin filaments. Complex communication pathways link the catalytic nucleotide-binding region, the structures responsible for force amplification and the actin-binding domain of myosin. We have crystallized the nucleotide-free motor domain of myosin II in a new conformation in which switch I and switch II, conserved loop structures involved in nucleotide binding, have moved away from the nucleotide-binding pocket. These movements are linked to rearrangements of the actin-binding region, which illuminate a previously unobserved communication pathway between the nucleotide-binding pocket and the actin-binding region, explain the reciprocal relationship between actin and nucleotide affinity and suggest a new mechanism for product release in myosin family motors.

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Figure 1: Three conformations of the myosin II nucleotide-binding pocket.
Figure 2: Global conformational changes in the O/O conformation of myosin II.
Figure 3

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Acknowledgements

We thank W. Kabsch for crystallographic advice, S. Zimmermann and A. Scherer for excellent technical assistance, S. Fujita-Becker for in vitro motility analysis and K.C. Holmes for helpful comments, discussions and continuous support. The work was supported by Molecular Motors project grants from the Deutsche Forschungsgemeinschaft.

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  1. Andreas Becker

    Present address: Department of Medicinal Chemistry, University of Kansas, 4040a Malott Hall, Lawrence, Kansas, 66045, USA

Authors and Affiliations

  1. Abteilung Biophysik, Max-Planck Institut für medizinische Forschung, Jahnstr. 29, Heidelberg, D-69120, Germany

    Thomas F Reubold, Susanne Eschenburg, Andreas Becker & Dietmar J Manstein

  2. Department of Chemistry, Dartmouth College, 6128 Burke Laboratory, Hanover, 03755, New Hampshire, USA

    F Jon Kull

  3. Institut für Biophysikalische Chemie, OE4350, Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, Hannover, 30623, Germany

    Dietmar J Manstein

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Correspondence to Dietmar J Manstein.

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Reubold, T., Eschenburg, S., Becker, A. et al. A structural model for actin-induced nucleotide release in myosin. Nat Struct Mol Biol 10, 826–830 (2003). https://doi.org/10.1038/nsb987

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