How Myosin Generates Force on Actin Filaments

Trends Biochem Sci. 2016 Dec;41(12):989-997. doi: 10.1016/j.tibs.2016.09.006. Epub 2016 Oct 4.

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.

Keywords: allostery; chemo-mechanical transduction; force generation; molecular motors.

Publication types

  • Review
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Cytoskeleton / metabolism
  • Actin Cytoskeleton / ultrastructure*
  • Actins / chemistry*
  • Actins / metabolism
  • Adenosine Diphosphate / chemistry*
  • Adenosine Diphosphate / metabolism
  • Adenosine Triphosphate / chemistry*
  • Adenosine Triphosphate / metabolism
  • Amino Acid Motifs
  • Binding Sites
  • Biomechanical Phenomena
  • Catalytic Domain
  • Fluorescence Resonance Energy Transfer
  • Humans
  • Mechanotransduction, Cellular
  • Myosins / chemistry*
  • Myosins / metabolism
  • Phosphates / chemistry*
  • Phosphates / metabolism
  • Protein Binding
  • Protein Conformation, alpha-Helical
  • Protein Conformation, beta-Strand
  • Protein Interaction Domains and Motifs

Substances

  • Actins
  • Phosphates
  • Adenosine Diphosphate
  • Adenosine Triphosphate
  • Myosins