Electron cryo-microscopy shows how strong binding of myosin to actin releases nucleotide

Nature. 2003 Sep 25;425(6956):423-7. doi: 10.1038/nature02005.

Abstract

Muscle contraction involves the cyclic interaction of the myosin cross-bridges with the actin filament, which is coupled to steps in the hydrolysis of ATP. While bound to actin each cross-bridge undergoes a conformational change, often referred to as the "power stroke", which moves the actin filament past the myosin filaments; this is associated with the release of the products of ATP hydrolysis and a stronger binding of myosin to actin. The association of a new ATP molecule weakens the binding again, and the attached cross-bridge rapidly dissociates from actin. The nucleotide is then hydrolysed, the conformational change reverses, and the myosin cross-bridge reattaches to actin. X-ray crystallography has determined the structural basis of the power stroke, but it is still not clear why the binding of actin weakens that of the nucleotide and vice versa. Here we describe, by fitting atomic models of actin and the myosin cross-bridge into high-resolution electron cryo-microscopy three-dimensional reconstructions, the molecular basis of this linkage. The closing of the actin-binding cleft when actin binds is structurally coupled to the opening of the nucleotide-binding pocket.

MeSH terms

  • Actin Cytoskeleton / chemistry
  • Actin Cytoskeleton / metabolism
  • Actin Cytoskeleton / ultrastructure
  • Actins / chemistry
  • Actins / metabolism*
  • Actins / ultrastructure*
  • Adenosine Triphosphate / metabolism*
  • Animals
  • Binding Sites
  • Chickens
  • Cryoelectron Microscopy*
  • Crystallography, X-Ray
  • Hydrolysis
  • Models, Molecular
  • Myosin Subfragments / chemistry
  • Myosin Subfragments / metabolism
  • Myosin Subfragments / ultrastructure
  • Myosins / chemistry
  • Myosins / metabolism*
  • Myosins / ultrastructure*
  • Protein Structure, Quaternary

Substances

  • Actins
  • Myosin Subfragments
  • Adenosine Triphosphate
  • Myosins