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

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...

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Bibliographic Details
Published in:Molecular cell 2009-08, Vol.35 (3), p.305-315
Main Authors: Mukherjea, Monalisa, Llinas, Paola, Kim, HyeongJun, Travaglia, Mirko, Safer, Daniel, Ménétrey, Julie, Franzini-Armstrong, Clara, Selvin, Paul R., Houdusse, Anne, Sweeney, H. Lee
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
CELLBIO
Dimerization
Models, Molecular
Molecular Sequence Data
Myosin Heavy Chains - chemistry
Myosin Heavy Chains - genetics
Myosin Heavy Chains - metabolism
Myosin Heavy Chains - physiology
Protein Folding
Protein Structure, Tertiary
PROTEINS
Sequence Deletion
Swine
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Summary: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.
ISSN:1097-2765
1097-4164
DOI:10.1016/j.molcel.2009.07.010