title: How Myosin Generates Force on Actin Filaments.
abstract: How myosin interacts with actin to generate force is a subject of considerable controversy. The major debate centers on understanding at what point in force generation the inorganic phosphate is released with respect to the lever arm swing, or powerstroke. Resolving the controversy is essential for understanding how force is produced as well as the mechanisms underlying disease-causing mutations in myosin. Recent structural insights into the powerstroke have come from a high-resolution structure of myosin in a previously unseen state and from an electron cryomicroscopy (cryo-EM) 3D reconstruction of the actin-myosin-MgADP complex. Here, we argue that seemingly contradictory data from time-resolved fluorescence resonance energy transfer (FRET) studies can be reconciled, and we put forward a model for myosin force generation on actin.
authors.affiliation: Structural Motility, Institut Curie, PSL Research University, CNRS, UMR 144, F-75005, Paris, France; Sorbonne Universités, UPMC Univ Paris06, Sorbonne Universités, IFD, 4 Place Jussieu, 75252 Paris cedex 05, France. Electronic address: anne.houdusse@curie.fr.
authors.forename: Anne
authors.initials: A
authors.lastname: Houdusse
authors.affiliation: Department of Pharmacology & Therapeutics and the Myology Institute, University of Florida College of Medicine, PO Box 100267, Gainesville, FL 32610-0267, USA. Electronic address: Lsweeney@ufl.edu.
authors.forename: H Lee
authors.initials: HL
authors.lastname: Sweeney
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism / Q000648:ultrastructure*; D000199:Actins / Q000737:chemistry* / Q000378:metabolism; D000244:Adenosine Diphosphate / Q000737:chemistry* / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000737:chemistry* / Q000378:metabolism; D020816:Amino Acid Motifs; D001665:Binding Sites; D001696:Biomechanical Phenomena; D020134:Catalytic Domain; D031541:Fluorescence Resonance Energy Transfer; D006801:Humans; D040542:Mechanotransduction, Cellular; D009218:Myosins / Q000737:chemistry* / Q000378:metabolism; D010710:Phosphates / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D000072756:Protein Conformation, alpha-Helical; D000072757:Protein Conformation, beta-Strand; D054730:Protein Interaction Domains and Motifs
chemical_list: D000199:Actins; D010710:Phosphates; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D009218:Myosins
keywords: allostery; chemo-mechanical transduction; force generation; molecular motors