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Myosin cleft movement and its coupling to actomyosin dissociation

Nature Structural & Molecular Biologyvolume 10pages831835 (2003) | Download Citation



It has long been known that binding of actin and binding of nucleotides to myosin are antagonistic, an observation that led to the biochemical basis for the crossbridge cycle of muscle contraction. Thus ATP binding to actomyosin causes actin dissociation, whereas actin binding to the myosin accelerates ADP and phosphate release. Structural studies have indicated that communication between the actin- and nucleotide-binding sites involves the opening and closing of the cleft between the upper and lower 50K domains of the myosin head. Here we test the proposal that the cleft responds to actin and nucleotide binding in a reciprocal manner and show that cleft movement is coupled to actin binding and dissociation. We monitored cleft movement using pyrene excimer fluorescence from probes engineered across the cleft.

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We thank W. Shih and J. Spudich for the cysteine-deficient construct and K. Holmes and R. Schroeder for the coordinates of their actomyosin model. We are grateful to the Wellcome Trust, the UK Biotechnology and Biological Sciences Research Council, the US National Science Foundation and the Magyary Zoltán Foundation for financial support.

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Author notes

    • Mihály Kovács

    Present address: Laboratory of Molecular Cardiology, National Heart, Lung and Blood Institute, Bethesda, Maryland, 20892-1762, USA


  1. Department of Biochemistry, University of Leicester, Leicester, LE1 7RH, UK

    • Paul B Conibear
    • , Clive R Bagshaw
    •  & András Málnási-Csizmadia
  2. Institute of Molecular Biophysics, Florida State University, Tallahassee, 32310, Florida, USA

    • Piotr G Fajer
  3. Department of Biochemistry, Eötvös University, Budapest, H-1117, Hungary

    • Mihály Kovács
    •  & András Málnási-Csizmadia


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The authors declare no competing financial interests.

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Correspondence to Clive R Bagshaw.

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