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

Julie Ménétrey, Amel Bahloul, Amber L. Wells, Christopher Yengo, Carl A. Morris, H. Lee Sweeney, Anne Houdusse

Research output: Contribution to journalArticle

157 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)779-785
Number of pages7
JournalNature
Volume435
Issue number7043
DOIs
StatePublished - Jun 9 2005

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Calmodulin
Myosins
Nucleotides
Kinesin
Actin Cytoskeleton
Binding Sites
myosin VI

All Science Journal Classification (ASJC) codes

  • General

Cite this

Ménétrey, J., Bahloul, A., Wells, A. L., Yengo, C., Morris, C. A., Sweeney, H. L., & Houdusse, A. (2005). The structure of the myosin VI motor reveals the mechanism of directionality reversal. Nature, 435(7043), 779-785. https://doi.org/10.1038/nature03592
Ménétrey, Julie ; Bahloul, Amel ; Wells, Amber L. ; Yengo, Christopher ; Morris, Carl A. ; Sweeney, H. Lee ; Houdusse, Anne. / The structure of the myosin VI motor reveals the mechanism of directionality reversal. In: Nature. 2005 ; Vol. 435, No. 7043. pp. 779-785.
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Ménétrey, J, Bahloul, A, Wells, AL, Yengo, C, Morris, CA, Sweeney, HL & Houdusse, A 2005, 'The structure of the myosin VI motor reveals the mechanism of directionality reversal', Nature, vol. 435, no. 7043, pp. 779-785. https://doi.org/10.1038/nature03592

The structure of the myosin VI motor reveals the mechanism of directionality reversal. / Ménétrey, Julie; Bahloul, Amel; Wells, Amber L.; Yengo, Christopher; Morris, Carl A.; Sweeney, H. Lee; Houdusse, Anne.

In: Nature, Vol. 435, No. 7043, 09.06.2005, p. 779-785.

Research output: Contribution to journalArticle

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Ménétrey J, Bahloul A, Wells AL, Yengo C, Morris CA, Sweeney HL et al. The structure of the myosin VI motor reveals the mechanism of directionality reversal. Nature. 2005 Jun 9;435(7043):779-785. https://doi.org/10.1038/nature03592