Reversible movement of switch 1 loop of myosin determines actin interaction

EMBO J. 2007 Jan 10;26(1):265-74. doi: 10.1038/sj.emboj.7601482.

Abstract

The conserved switch 1 loop of P-loop NTPases is implicated as a central element that transmits information between the nucleotide-binding pocket and the binding site of the partner proteins. Recent structural studies have identified two states of switch 1 in G-proteins and myosin, but their role in the transduction mechanism has yet to be clarified. Single tryptophan residues were introduced into the switch 1 region of myosin II motor domain and studied by rapid reaction methods. We found that in the presence of MgADP, two states of switch 1 exist in dynamic equilibrium. Actin binding shifts the equilibrium towards one of the MgADP states, whereas ATP strongly favors the other. In the light of electron cryo-microscopic and X-ray crystallographic results, these findings lead to a specific structural model in which the equilibrium constant between the two states of switch 1 is coupled to the strength of the actin-myosin interaction. This has implications for the enzymatic mechanism of G-proteins and possibly P-loop NTPases in general.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / chemistry*
  • Adenosine Diphosphate / chemistry
  • Adenosine Triphosphate / chemistry
  • Animals
  • Cryoelectron Microscopy
  • Crystallography, X-Ray
  • Dictyostelium
  • Magnesium / chemistry
  • Models, Chemical
  • Models, Molecular
  • Myosins / chemistry*
  • Protein Binding
  • Protein Conformation
  • Protein Structure, Tertiary
  • Tryptophan / chemistry

Substances

  • Actins
  • Adenosine Diphosphate
  • Tryptophan
  • Adenosine Triphosphate
  • Myosins
  • Magnesium