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 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.
Mukherjea
Monalisa
M
Department of Physiology, University of Pennsylvania School of Medicine, Philadelphia, 19104, USA.
Llinas
Paola
P
Kim
HyeongJun
H
Travaglia
Mirko
M
Safer
Daniel
D
Ménétrey
Julie
J
Franzini-Armstrong
Clara
C
Selvin
Paul R
PR
Houdusse
Anne
A
Sweeney
H Lee
HL
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
C089785:myosin VI; D018995:Myosin Heavy Chains