title: Myosin VI is an actin-based motor that moves backwards.
abstract: Myosins and kinesins are molecular motors that hydrolyse ATP to track along actin filaments and microtubules, respectively. Although the kinesin family includes motors that move towards either the plus or minus ends of microtubules, all characterized myosin motors move towards the barbed (+) end of actin filaments. Crystal structures of myosin II (refs 3-6) have shown that small movements within the myosin motor core are transmitted through the 'converter domain' to a 'lever arm' consisting of a light-chain-binding helix and associated light chains. The lever arm further amplifies the motions of the converter domain into large directed movements. Here we report that myosin VI, an unconventional myosin, moves towards the pointed (-) end of actin. We visualized the myosin VI construct bound to actin using cryo-electron microscopy and image analysis, and found that an ADP-mediated conformational change in the domain distal to the motor, a structure likely to be the effective lever arm, is in the opposite direction to that observed for other myosins. Thus, it appears that myosin VI achieves reverse-direction movement by rotating its lever arm in the opposite direction to conventional myosin lever arm movement.
authors.affiliation: Department of Physiology, University of Pennsylvania School of Medicine, Philadelphia 19104-6085, USA.
authors.forename: A L
authors.initials: AL
authors.lastname: Wells
authors.forename: A W
authors.initials: AW
authors.lastname: Lin
authors.forename: L Q
authors.initials: LQ
authors.lastname: Chen
authors.forename: D
authors.initials: D
authors.lastname: Safer
authors.forename: S M
authors.initials: SM
authors.lastname: Cain
authors.forename: T
authors.initials: T
authors.lastname: Hasson
authors.forename: B O
authors.initials: BO
authors.lastname: Carragher
authors.forename: R A
authors.initials: RA
authors.lastname: Milligan
authors.forename: H L
authors.initials: HL
authors.lastname: Sweeney
mesh_terms: D000199:Actins / Q000502:physiology* / Q000648:ultrastructure; D000244:Adenosine Diphosphate / Q000378:metabolism; D000818:Animals; D001696:Biomechanical Phenomena; D002147:Calmodulin / Q000378:metabolism; D020285:Cryoelectron Microscopy; D006801:Humans; D020409:Molecular Motor Proteins; D018995:Myosin Heavy Chains / Q000235:genetics / Q000502:physiology* / Q000648:ultrastructure; D011994:Recombinant Proteins / Q000378:metabolism; D013552:Swine
chemical_list: D000199:Actins; D002147:Calmodulin; D020409:Molecular Motor Proteins; D011994:Recombinant Proteins; C089785:myosin VI; D000244:Adenosine Diphosphate; D018995:Myosin Heavy Chains