The kinetic mechanism of mouse myosin VIIA

J Biol Chem. 2011 Mar 18;286(11):8819-28. doi: 10.1074/jbc.M110.163592. Epub 2011 Jan 6.

Abstract

Myosin VIIa is crucial in hearing and visual processes. We examined the kinetic and association properties of the baculovirus expressed, truncated mouse myosin VIIa construct containing the head, all 5IQ motifs and the putative coiled coil domain (myosin VIIa-5IQ). The construct appears to be monomeric as determined by analytical ultracentrifugation experiments, and only single headed molecules were detected by negative stain electron microscopy. The relatively high basal steady-state rate of 0.18 s(-1) is activated by actin only by ∼3.5-fold resulting in a V(max) of 0.7 s(-1) and a K(ATPase) of 11.5 μM. There is no single rate-limiting step of the ATP hydrolysis cycle. The ATP hydrolysis step (M·T M·D·P) is slow (12 s(-1)) and the equilibrium constant (K(H)) of 1 suggests significant reversal of hydrolysis. In the presence of actin ADP dissociates with a rate constant of 1.2 s(-1). Phosphate dissociation is relatively fast (>12 s(-1)), but the maximal rate could not be experimentally obtained at actin concentrations ≤ 50 μM because of the weak binding of the myosin VIIa-ADP-P(i) complex to actin. At higher actin concentrations the rate of attached hydrolysis (0.4 s(-1)) becomes significant and partially rate-limiting. Our findings suggest that the myosin VIIa is a "slow", monomeric molecular motor with a duty ratio of 0.6.

Publication types

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

MeSH terms

  • Adenosine Triphosphate / chemistry*
  • Adenosine Triphosphate / genetics
  • Adenosine Triphosphate / metabolism
  • Amino Acid Motifs
  • Animals
  • Kinetics
  • Mice
  • Myosin VIIa
  • Myosins / chemistry*
  • Myosins / genetics
  • Myosins / metabolism
  • Protein Structure, Tertiary

Substances

  • Myo7a protein, mouse
  • Myosin VIIa
  • Adenosine Triphosphate
  • Myosins