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  • The EMBO Journal (2007) 26, 2682 - 2692
  • doi:10.1038/sj.emboj.7601720

Published online: 17 May 2007

How myosin VI coordinates its heads during processive movement

H Lee Sweeney1, Hyokeun Park2, Alan B Zong1, Zhaohui Yang1, Paul R Selvin3,4 and Steven S Rosenfeld5

  1. Department of Physiology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
  2. Department of Chemistry, University of Illinois, Urbana, IL, USA
  3. Department of Physics, University of Illinois, Urbana, IL, USA
  4. Center for Biophysics and Computational Biology, University of Illinois, Urbana, IL, USA
  5. The Neurological Institute of New York, Columbia University, New York, NY, USA

Correspondence to:

Steven S Rosenfeld, The Neurological Institute of New York, Columbia University, 710 West 168th Street, New York, NY 10032, USA. Tel.: +1 212 305 1718; Fax: +1 212 305 1716; E-mail: sr2327@columbia.edu

Received 28 October 2006; Accepted 17 April 2007

A processive molecular motor must coordinate the enzymatic state of its two catalytic domains in order to prevent premature detachment from its track. For myosin V, internal strain produced when both heads of are attached to an actin track prevents completion of the lever arm swing of the lead head and blocks ADP release. However, this mechanism cannot work for myosin VI, since its lever arm positions are reversed. Here, we demonstrate that myosin VI gating is achieved instead by blocking ATP binding to the lead head once it has released its ADP. The structural basis for this unique gating mechanism involves an insert near the nucleotide binding pocket that is found only in class VI myosin. Reverse strain greatly favors binding of ADP to the lead head, which makes it possible for myosin VI to function as a processive transporter as well as an actin-based anchor. While this mechanism is unlike that of any other myosin superfamily member, it bears remarkable similarities to that of another processive motor from a different superfamily—kinesin I.

  • Keywords:

    • gating,
    • kinetics,
    • motility,
    • processivity,
    • unconventional myosin