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Myosin VI is an actin-based motor that moves backwards

Author

Listed:
  • Amber L. Wells

    (University of Pennsylvania School of Medicine)

  • Abel W. Lin

    (The Scripps Research Institute)

  • Li-Qiong Chen

    (University of Pennsylvania School of Medicine)

  • Daniel Safer

    (University of Pennsylvania School of Medicine)

  • Shane M. Cain

    (University of California)

  • Tama Hasson

    (University of California)

  • Bridget O. Carragher

    (Beckman Institute, Dept. of Cell and Structural Biology, University of Illinois at Urbana-Champaign)

  • Ronald A. Milligan

    (The Scripps Research Institute)

  • H. Lee Sweeney

    (University of Pennsylvania School of Medicine)

Abstract

Myosins and kinesins are molecular motors that hydrolyse ATP to track along actin filaments and microtubules, respectively. Although the kinesin family includes motors that move towards either the plus or minus ends of microtubules1, all characterized myosin motors move towards the barbed (+) end of actin filaments2. Crystal structures of myosin II (refs 3,4,5,6) have shown that small movements within the myosin motor core are transmitted through the ‘converter domain’ to a ‘lever arm’ consisting of a light-chain-binding helix and associated light chains5,6. The lever arm further amplifies the motions of the converter domain into large directed movements3,5,6,7. Here we report that myosin VI, an unconventional myosin8,9,10,11,12, moves towards the pointed (-) end of actin. We visualized the myosin VI construct bound to actin using cryo-electron microscopy and image analysis, and found that an ADP-mediated conformational change in the domain distal to the motor, a structure likely to be the effective lever arm, is in the opposite direction to that observed for other myosins. Thus, it appears that myosin VI achieves reverse-direction movement by rotating its lever arm in the opposite direction to conventional myosin lever arm movement.

Suggested Citation

  • Amber L. Wells & Abel W. Lin & Li-Qiong Chen & Daniel Safer & Shane M. Cain & Tama Hasson & Bridget O. Carragher & Ronald A. Milligan & H. Lee Sweeney, 1999. "Myosin VI is an actin-based motor that moves backwards," Nature, Nature, vol. 401(6752), pages 505-508, September.
    • Handle: RePEc:nat:nature:v:401:y:1999:i:6752:d:10.1038_46835
    DOI: 10.1038/46835
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    Cited by:

    1. Jie Shi & Kristine Hauschulte & Ivan Mikicic & Srijana Maharjan & Valerie Arz & Tina Strauch & Jan B. Heidelberger & Jonas V. Schaefer & Birgit Dreier & Andreas Plückthun & Petra Beli & Helle D. Ulric, 2023. "Nuclear myosin VI maintains replication fork stability," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    2. Alastair Skeffington & Axel Fischer & Sanja Sviben & Magdalena Brzezinka & Michał Górka & Luca Bertinetti & Christian Woehle & Bruno Huettel & Alexander Graf & André Scheffel, 2023. "A joint proteomic and genomic investigation provides insights into the mechanism of calcification in coccolithophores," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    3. Fengfeng Niu & Lingxuan Li & Lei Wang & Jinman Xiao & Shun Xu & Yong Liu & Leishu Lin & Cong Yu & Zhiyi Wei, 2024. "Autoinhibition and activation of myosin VI revealed by its cryo-EM structure," Nature Communications, Nature, vol. 15(1), pages 1-13, December.

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