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Simultaneous Observation of the Lever Arm and Head Explains Myosin VI Dual Function

Authors

  • Keigo Ikezaki,

    1. Graduate School of Frontier Biosciences, Osaka University, 1–3 Yamadaoka, Suita, Osaka, 565-0871, Japan
    2. Quantitative Biology Center (QBiC), RIKEN, Furuedai, Suita, Osaka, 565-0874, Japan
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  • Tomotaka Komori,

    Corresponding author
    1. Graduate School of Frontier Biosciences, Osaka University, 1–3 Yamadaoka, Suita, Osaka, 565-0871, Japan
    • Graduate School of Frontier Biosciences, Osaka University, 1–3 Yamadaoka, Suita, Osaka, 565-0871, Japan.
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  • Mitsuhiro Sugawa,

    1. Graduate School of Frontier Biosciences, Osaka University, 1–3 Yamadaoka, Suita, Osaka, 565-0871, Japan
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  • Yoshiyuki Arai,

    1. Graduate School of Frontier Biosciences, Osaka University, 1–3 Yamadaoka, Suita, Osaka, 565-0871, Japan
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  • So Nishikawa,

    1. Graduate School of Frontier Biosciences, Osaka University, 1–3 Yamadaoka, Suita, Osaka, 565-0871, Japan
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  • Atsuko H. Iwane,

    1. Graduate School of Frontier Biosciences, Osaka University, 1–3 Yamadaoka, Suita, Osaka, 565-0871, Japan
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  • Toshio Yanagida

    Corresponding author
    1. Graduate School of Frontier Biosciences, Osaka University, 1–3 Yamadaoka, Suita, Osaka, 565-0871, Japan
    2. Quantitative Biology Center (QBiC), RIKEN, Furuedai, Suita, Osaka, 565-0874, Japan
    3. Center for Information and Neural Networks (CiNet), Yamadaoka, Suita, Osaka, 565-0871, Japan
    4. WPI, Immunology Frontier Research Center, Osaka University, Yamadaoka, Suita, Osaka, 565-0871, Japan
    • Graduate School of Frontier Biosciences, Osaka University, 1–3 Yamadaoka, Suita, Osaka, 565-0871, Japan.
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Abstract

Myosin VI is an adenosine triphosphate (ATP)-driven dimeric molecular motor that has dual function as a vesicle transporter and a cytoskeletal anchor. Recently, it was reported that myosin VI generates three types of steps by taking either a distant binding or adjacent binding state (noncanonical hand-over-hand step pathway). The adjacent binding state, in which both heads bind to an actin filament near one another, is unique to myosin VI and therefore may help explain its distinct features. However, detailed information of the adjacent binding state remains unclear. Here simultaneous observations of the head and tail domain during stepping are presented. These observations show that the lever arms tilt forward in the adjacent binding state. Furthermore, it is revealed that either head could take the subsequent step with equal probability from this state. Together with previous results, a comprehensive stepping scheme is proposed; it includes the tail domain motion to explain how myosin VI achieves its dual function.

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