title: Force-producing ADP state of myosin bound to actin.
abstract: Molecular motors produce force when they interact with their cellular tracks. For myosin motors, the primary force-generating state has MgADP tightly bound, whereas myosin is strongly bound to actin. We have generated an 8-Å cryoEM reconstruction of this state for myosin V and used molecular dynamics flexed fitting for model building. We compare this state to the subsequent state on actin (Rigor). The ADP-bound structure reveals that the actin-binding cleft is closed, even though MgADP is tightly bound. This state is accomplished by a previously unseen conformation of the β-sheet underlying the nucleotide pocket. The transition from the force-generating ADP state to Rigor requires a 9.5° rotation of the myosin lever arm, coupled to a β-sheet rearrangement. Thus, the structure reveals the detailed rearrangements underlying myosin force generation as well as the basis of strain-dependent ADP release that is essential for processive myosins, such as myosin V.
authors.affiliation: Cryo Electron Microscopy, CellNetworks, BioQuant, Universitätsklinikum Heidelberg, 69120 Heidelberg, Germany;
authors.forename: Sarah F
authors.initials: SF
authors.lastname: Wulf
authors.affiliation: Structural Motility, Institut Curie, Paris Sciences et Lettres Research University, CNRS, UMR 144, F-75005, Paris, France;
authors.forename: Virginie
authors.initials: V
authors.lastname: Ropars
authors.affiliation: Cryo Electron Microscopy, CellNetworks, BioQuant, Universitätsklinikum Heidelberg, 69120 Heidelberg, Germany;
authors.forename: Setsuko
authors.initials: S
authors.lastname: Fujita-Becker
authors.affiliation: Cryo Electron Microscopy, CellNetworks, BioQuant, Universitätsklinikum Heidelberg, 69120 Heidelberg, Germany;
authors.forename: Marco
authors.initials: M
authors.lastname: Oster
authors.affiliation: Cryo Electron Microscopy, CellNetworks, BioQuant, Universitätsklinikum Heidelberg, 69120 Heidelberg, Germany;
authors.forename: Goetz
authors.initials: G
authors.lastname: Hofhaus
authors.affiliation: Protein Evolution, CellNetworks, BioQuant, Universität Heidelberg, 69120 Heidelberg, Germany;
authors.forename: Leonardo G
authors.initials: LG
authors.lastname: Trabuco
authors.affiliation: Structural Motility, Institut Curie, Paris Sciences et Lettres Research University, CNRS, UMR 144, F-75005, Paris, France;
authors.forename: Olena
authors.initials: O
authors.lastname: Pylypenko
authors.affiliation: Department of Pharmacology & Therapeutics, University of Florida College of Medicine, Gainesville, FL 32610 anne.houdusse@curie.fr Lsweeney@ufl.edu rasmus.schroeder@bioquant.uni-heidelberg.de.
authors.forename: H Lee
authors.initials: HL
authors.lastname: Sweeney
authors.affiliation: Structural Motility, Institut Curie, Paris Sciences et Lettres Research University, CNRS, UMR 144, F-75005, Paris, France; anne.houdusse@curie.fr Lsweeney@ufl.edu rasmus.schroeder@bioquant.uni-heidelberg.de.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Houdusse
authors.affiliation: Cryo Electron Microscopy, CellNetworks, BioQuant, Universitätsklinikum Heidelberg, 69120 Heidelberg, Germany; anne.houdusse@curie.fr Lsweeney@ufl.edu rasmus.schroeder@bioquant.uni-heidelberg.de.
authors.forename: Rasmus R
authors.initials: RR
authors.lastname: Schröder
mesh_terms: D000199:Actins / Q000737:chemistry / Q000378:metabolism*; D000244:Adenosine Diphosphate / Q000378:metabolism*; D001665:Binding Sites; D020285:Cryoelectron Microscopy; D018360:Crystallography, X-Ray; D006801:Humans; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D024701:Myosin Type V / Q000737:chemistry* / Q000378:metabolism*; D011487:Protein Conformation
chemical_list: D000199:Actins; D000244:Adenosine Diphosphate; D024701:Myosin Type V
keywords: force generation; molecular motor; myosin V; transducer