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Myosin VI is an actin-based motor that moves backwards

Nature volume 401, pages 505–508 (1999)Cite this article

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.

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Figure 1: Myosin VI.
Figure 2: Determination of direction of myosin movement.
Figure 3: Comparison of ADP (left) and rigor (right) 3D maps of myosin VI ( a, b), and smooth muscle myosin II (c, d) attached to F-actin.

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Acknowledgements

This work was supported by grants from the NIH. We thank M. S. Mooseker for the chicken myosin V cDNA, and G. Daniels of Leica Microsystems for technical support.

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Author notes

  1. H. Lee Sweeney: Correspondendence and requests for materials should be addressed to H.L.S.

Authors and Affiliations

  1. Department of Physiology, University of Pennsylvania School of Medicine, 3700 Hamilton Walk, Philadelphia, 19104-6085, Pennsylvania, USA

    Amber L. Wells, Li-Qiong Chen, Daniel Safer & H. Lee Sweeney

  2. Department of Cell Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, 92037, California, USA

    Abel W. Lin & Ronald A. Milligan

  3. Department of Biology, University of California, San Diego, La Jolla, 92093-0368, California , USA

    Shane M. Cain & Tama Hasson

  4. Beckman Institute, Dept. of Cell and Structural Biology, University of Illinois at Urbana-Champaign, Urbana, 61801, Illinois, USA

    Bridget O. Carragher

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Wells, A., Lin, A., Chen, LQ. et al. Myosin VI is an actin-based motor that moves backwards. Nature 401, 505–508 (1999). https://doi.org/10.1038/46835

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