Structural transitions of F-actin upon ATP hydrolysis at near-atomic resolution revealed by cryo-EM

Nat Struct Mol Biol. 2018 Jun;25(6):528-537. doi: 10.1038/s41594-018-0074-0. Epub 2018 Jun 4.


The function of actin is coupled to the nucleotide bound to its active site. ATP hydrolysis is activated during polymerization; a delay between hydrolysis and inorganic phosphate (Pi) release results in a gradient of ATP, ADP-Pi and ADP along actin filaments (F-actin). Actin-binding proteins can recognize F-actin's nucleotide state, using it as a local 'age' tag. The underlying mechanism is complex and poorly understood. Here we report six high-resolution cryo-EM structures of F-actin from rabbit skeletal muscle in different nucleotide states. The structures reveal that actin polymerization repositions the proposed catalytic base, His161, closer to the γ-phosphate. Nucleotide hydrolysis and Pi release modulate the conformational ensemble at the periphery of the filament, thus resulting in open and closed states, which can be sensed by coronin-1B. The drug-like toxin jasplakinolide locks F-actin in an open state. Our results demonstrate in detail how ATP hydrolysis links to F-actin's conformational dynamics and protein interaction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4-Butyrolactone / analogs & derivatives
  • 4-Butyrolactone / metabolism
  • Actins / chemistry*
  • Actins / metabolism
  • Adenosine Diphosphate / metabolism
  • Adenosine Triphosphate / metabolism*
  • Animals
  • Cryoelectron Microscopy
  • Depsipeptides / metabolism
  • Hydrolysis
  • Microfilament Proteins / metabolism
  • Muscle, Skeletal / metabolism
  • Phosphates / metabolism
  • Protein Binding
  • Protein Conformation
  • Rabbits


  • Actins
  • Depsipeptides
  • Microfilament Proteins
  • Phosphates
  • coronin
  • jasplakinolide
  • Adenosine Diphosphate
  • Adenosine Triphosphate
  • 4-Butyrolactone