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The structure of the myosin VI motor reveals the mechanism of directionality reversal

Author

Listed:
  • Julie Ménétrey

    (Institut Curie CNRS, UMR144)

  • Amel Bahloul

    (Institut Curie CNRS, UMR144)

  • Amber L. Wells

    (University of Pennsylvania School of Medicine)

  • Christopher M. Yengo

    (University of Pennsylvania School of Medicine)

  • Carl A. Morris

    (University of Pennsylvania School of Medicine)

  • H. Lee Sweeney

    (University of Pennsylvania School of Medicine)

  • Anne Houdusse

    (Institut Curie CNRS, UMR144)

Abstract

Here we solve a 2.4-Å structure of a truncated version of the reverse-direction myosin motor, myosin VI, that contains the motor domain and binding sites for two calmodulin molecules. The structure reveals only minor differences in the motor domain from that in plus-end directed myosins, with the exception of two unique inserts. The first is near the nucleotide-binding pocket and alters the rates of nucleotide association and dissociation. The second unique insert forms an integral part of the myosin VI converter domain along with a calmodulin bound to a novel target motif within the insert. This serves to redirect the effective ‘lever arm’ of myosin VI, which includes a second calmodulin bound to an ‘IQ motif’, towards the pointed (minus) end of the actin filament. This repositioning largely accounts for the reverse directionality of this class of myosin motors. We propose a model incorporating a kinesin-like uncoupling/docking mechanism to provide a full explanation of the movements of myosin VI.

Suggested Citation

  • Julie Ménétrey & Amel Bahloul & Amber L. Wells & Christopher M. Yengo & Carl A. Morris & H. Lee Sweeney & Anne Houdusse, 2005. "The structure of the myosin VI motor reveals the mechanism of directionality reversal," Nature, Nature, vol. 435(7043), pages 779-785, June.
  • Handle: RePEc:nat:nature:v:435:y:2005:i:7043:d:10.1038_nature03592
    DOI: 10.1038/nature03592
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    Cited by:

    1. Janeska J. Jonge & Andreas Graw & Vasileios Kargas & Christopher Batters & Antonino F. Montanarella & Tom O’Loughlin & Chloe Johnson & Susan D. Arden & Alan J. Warren & Michael A. Geeves & John Kendri, 2024. "Motor domain phosphorylation increases nucleotide exchange and turns MYO6 into a faster and stronger motor," Nature Communications, Nature, vol. 15(1), pages 1-18, December.

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