Myosin VI Dimerization Triggers an Unfolding of a Three-Helix Bundle in Order to Extend Its Reach

Monalisa Mukherjea, Paola Llinas, Hyeong Jun Kim, Mirko Travaglia, Daniel Safer, Julie Ménétrey, Clara Franzini-Armstrong, Paul R Selvin, Anne Houdusse, H. Lee Sweeney

Research output: Contribution to journalArticle

Abstract

Myosin VI challenges the prevailing theory of how myosin motors move on actin: the lever arm hypothesis. While the reverse directionality and large powerstroke of myosin VI can be attributed to unusual properties of a subdomain of the motor (converter with a unique insert), these adaptations cannot account for the large step size on actin. Either the lever arm hypothesis needs modification, or myosin VI has some unique form of extension of its lever arm. We determined the structure of the region immediately distal to the lever arm of the motor and show that it is a three-helix bundle. Based on C-terminal truncations that display the normal range of step sizes on actin, CD, fluorescence studies, and a partial deletion of the bundle, we demonstrate that this bundle unfolds upon dimerization of two myosin VI monomers. This unconventional mechanism generates an extension of the lever arm of myosin VI.

Original languageEnglish (US)
Pages (from-to)305-315
Number of pages11
JournalMolecular cell
Volume35
Issue number3
DOIs
StatePublished - Aug 14 2009

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Dimerization
Actins
Myosins
Reference Values
Fluorescence
myosin VI

Keywords

  • CELLBIO
  • PROTEINS

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Mukherjea, M., Llinas, P., Kim, H. J., Travaglia, M., Safer, D., Ménétrey, J., ... Sweeney, H. L. (2009). Myosin VI Dimerization Triggers an Unfolding of a Three-Helix Bundle in Order to Extend Its Reach. Molecular cell, 35(3), 305-315. https://doi.org/10.1016/j.molcel.2009.07.010

Myosin VI Dimerization Triggers an Unfolding of a Three-Helix Bundle in Order to Extend Its Reach. / Mukherjea, Monalisa; Llinas, Paola; Kim, Hyeong Jun; Travaglia, Mirko; Safer, Daniel; Ménétrey, Julie; Franzini-Armstrong, Clara; Selvin, Paul R; Houdusse, Anne; Sweeney, H. Lee.

In: Molecular cell, Vol. 35, No. 3, 14.08.2009, p. 305-315.

Research output: Contribution to journalArticle

Mukherjea, M, Llinas, P, Kim, HJ, Travaglia, M, Safer, D, Ménétrey, J, Franzini-Armstrong, C, Selvin, PR, Houdusse, A & Sweeney, HL 2009, 'Myosin VI Dimerization Triggers an Unfolding of a Three-Helix Bundle in Order to Extend Its Reach', Molecular cell, vol. 35, no. 3, pp. 305-315. https://doi.org/10.1016/j.molcel.2009.07.010
Mukherjea M, Llinas P, Kim HJ, Travaglia M, Safer D, Ménétrey J et al. Myosin VI Dimerization Triggers an Unfolding of a Three-Helix Bundle in Order to Extend Its Reach. Molecular cell. 2009 Aug 14;35(3):305-315. https://doi.org/10.1016/j.molcel.2009.07.010
Mukherjea, Monalisa ; Llinas, Paola ; Kim, Hyeong Jun ; Travaglia, Mirko ; Safer, Daniel ; Ménétrey, Julie ; Franzini-Armstrong, Clara ; Selvin, Paul R ; Houdusse, Anne ; Sweeney, H. Lee. / Myosin VI Dimerization Triggers an Unfolding of a Three-Helix Bundle in Order to Extend Its Reach. In: Molecular cell. 2009 ; Vol. 35, No. 3. pp. 305-315.
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