Article

  • The EMBO Journal (2004) 23, 1729 - 1738
  • doi:10.1038/sj.emboj.7600180

Published online: 25 March 2004

A monomeric myosin VI with a large working stroke

Ida Lister1, Stephan Schmitz2, Matthew Walker3, John Trinick3, Folma Buss4, Claudia Veigel2 and John Kendrick-Jones1

  1. MRC Laboratory of Molecular Biology, Hills Road, Cambridge, UK
  2. Division of Physical Biochemistry, NIMR, The Ridgeway, Mill Hill, London, UK
  3. School of Biomedical Sciences, University of Leeds, Leeds, UK
  4. Cambridge Institute for Medical Research, University of Cambridge, Wellcome Trust/MRC Building, Hills Road, Cambridge, UK

Correspondence to:

John Kendrick-Jones, MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK. Tel.: +44 1223 402409; Fax: +44 1223 213556; E-mail: jkj@mrc-lmb.cam.ac.uk

Received 20 November 2003; Accepted 1 March 2004


Myosin VI is involved in a wide variety of intracellular processes such as endocytosis, secretion and cell migration. Unlike almost all other myosins so far studied, it moves towards the minus end of actin filaments and is therefore likely to have unique cellular properties. However, its mechanism of force production and movement is not understood. Under our experimental conditions, both expressed full-length and native myosin VI are monomeric. Electron microscopy using negative staining revealed that the addition of ATP induces a large conformational change in the neck/tail region of the expressed molecule. Using an optical tweezers-based force transducer we found that expressed myosin VI is nonprocessive and produces a large working stroke of 18 nm. Since the neck region of myosin VI is short (it contains only a single IQ motif), it is difficult to reconcile the 18 nm working stroke with the classical 'lever arm mechanism', unless other structures in the molecule contribute to the effective lever. A possible model to explain the large working stroke of myosin VI is presented.

  • Keywords:

    • actin,
    • motility,
    • myosin,
    • working stroke
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