title: Processive steps in the reverse direction require uncoupling of the lead head lever arm of myosin VI.
abstract: Myosin VI is the only known reverse-direction myosin motor. It has an unprecedented means of amplifying movements within the motor involving rearrangements of the converter subdomain at the C terminus of the motor and an unusual lever arm projecting from the converter. While the average step size of a myosin VI dimer is 30-36 nm, the step size is highly variable, presenting a challenge to the lever arm mechanism by which all myosins are thought to move. Herein, we present structures of myosin VI that reveal regions of compliance that allow an uncoupling of the lead head when movement is modeled on actin. The location of the compliance restricts the possible actin binding sites and predicts the observed stepping behavior. The model reveals that myosin VI, unlike plus-end directed myosins, does not use a pure lever arm mechanism, but instead steps with a mechanism analogous to the kinesin neck-linker uncoupling model.
authors.affiliation: Structural Motility, Institut Curie, Centre de Recherche, Paris, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Ménétrey
authors.forename: Tatiana
authors.initials: T
authors.lastname: Isabet
authors.forename: Virginie
authors.initials: V
authors.lastname: Ropars
authors.forename: Monalisa
authors.initials: M
authors.lastname: Mukherjea
authors.forename: Olena
authors.initials: O
authors.lastname: Pylypenko
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Liu
authors.forename: Javier
authors.initials: J
authors.lastname: Perez
authors.forename: Patrice
authors.initials: P
authors.lastname: Vachette
authors.forename: H Lee
authors.initials: HL
authors.lastname: Sweeney
authors.forename: Anne M
authors.initials: AM
authors.lastname: Houdusse
mesh_terms: D000199:Actins / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D055592:Biophysical Phenomena; D002147:Calmodulin / Q000737:chemistry / Q000378:metabolism; D003187:Compliance; D018360:Crystallography, X-Ray; D008954:Models, Biological; D008958:Models, Molecular; D020409:Molecular Motor Proteins / Q000737:chemistry* / Q000378:metabolism*; D046912:Multiprotein Complexes / Q000737:chemistry / Q000378:metabolism; D018995:Myosin Heavy Chains / Q000737:chemistry* / Q000378:metabolism*; D009218:Myosins / Q000737:chemistry / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D013552:Swine
chemical_list: D000199:Actins; D002147:Calmodulin; D020409:Molecular Motor Proteins; D046912:Multiprotein Complexes; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; C089785:myosin VI; D018995:Myosin Heavy Chains; D009218:Myosins