title: Myosin VI dimerization triggers an unfolding of a three-helix bundle in order to extend its reach.
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.
authors: Department of Physiology, University of Pennsylvania School of Medicine, Philadelphia, 19104, USA.
authors: Monalisa
authors: M
authors: Mukherjea
authors: Paola
authors: P
authors: Llinas
authors: HyeongJun
authors: H
authors: Kim
authors: Mirko
authors: M
authors: Travaglia
authors: Daniel
authors: D
authors: Safer
authors: Julie
authors: J
authors: Ménétrey
authors: Clara
authors: C
authors: Franzini-Armstrong
authors: Paul R
authors: PR
authors: Selvin
authors: Anne
authors: A
authors: Houdusse
authors: H Lee
authors: HL
authors: Sweeney
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019281:Dimerization; D008958:Models, Molecular; D008969:Molecular Sequence Data; D018995:Myosin Heavy Chains / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D017384:Sequence Deletion; D013552:Swine
chemical_list: C089785:myosin VI; D018995:Myosin Heavy Chains