Three-dimensional structure of the myosin V inhibited state by cryoelectron tomography

Nature. 2006 Jul 13;442(7099):208-11. doi: 10.1038/nature04719. Epub 2006 Apr 16.

Abstract

Unconventional myosin V (myoV) is an actin-based molecular motor that has a key function in organelle and mRNA transport, as well as in membrane trafficking. MyoV was the first member of the myosin superfamily shown to be processive, meaning that a single motor protein can 'walk' hand-over-hand along an actin filament for many steps before detaching. Full-length myoV has a low actin-activated MgATPase activity at low [Ca2+], whereas expressed constructs lacking the cargo-binding domain have a high activity regardless of [Ca2+] (refs 5-7). Hydrodynamic data and electron micrographs indicate that the active state is extended, whereas the inactive state is compact. Here we show the first three-dimensional structure of the myoV inactive state. Each myoV molecule consists of two heads that contain an amino-terminal motor domain followed by a lever arm that binds six calmodulins. The heads are followed by a coiled-coil dimerization domain (S2) and a carboxy-terminal globular cargo-binding domain. In the inactive structure, bending of myoV at the head-S2 junction places the cargo-binding domain near the motor domain's ATP-binding pocket, indicating that ATPase inhibition might occur through decreased rates of nucleotide exchange. The actin-binding interfaces are unobstructed, and the lever arm is oriented in a position typical of strong actin-binding states. This structure indicates that motor recycling after cargo delivery might occur through transport on actively treadmilling actin filaments rather than by diffusion.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Actins / chemistry
  • Actins / metabolism
  • Actins / ultrastructure
  • Animals
  • Cryoelectron Microscopy*
  • Diffusion
  • Mice
  • Models, Molecular
  • Myosin Type V / antagonists & inhibitors*
  • Myosin Type V / chemistry
  • Myosin Type V / ultrastructure*
  • Protein Structure, Quaternary
  • Protein Structure, Tertiary

Substances

  • Actins
  • Myosin Type V

Associated data

  • PDB/2DFS