Load-dependent mechanism of nonmuscle myosin 2

Proc Natl Acad Sci U S A. 2007 Jun 12;104(24):9994-9. doi: 10.1073/pnas.0701181104. Epub 2007 Jun 4.


Loads on molecular motors regulate and coordinate their function. In a study that directly measures properties of internally strained myosin 2 heads bound to actin, we find that human nonmuscle myosins 2A and 2B show marked load-dependent changes in kinetics of ADP release but not in nucleotide binding. We show that the ADP release rate constant is increased 4-fold by the assisting load on one head and decreased 5-fold (for 2A) or 12-fold (for 2B) by the resisting load on the other. Thus these myosins, especially 2B, have marked mechanosensitivity of product release. By regulating the actin attachment of myosin heads, this provides a basis for energy-efficient tension maintenance without obstructing cellular contractility driven by other motors such as smooth muscle myosin. Whereas forward load accelerates the cycle of interaction with actin, resistive load increases duty ratio to favor tension maintenance by two-headed attachment.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Adenosine Diphosphate / metabolism
  • Adenosine Triphosphate / metabolism
  • Biomechanical Phenomena
  • Humans
  • Kinetics
  • Models, Biological
  • Molecular Motor Proteins / chemistry
  • Molecular Motor Proteins / metabolism
  • Myosin Subfragments / metabolism
  • Myosin Subfragments / ultrastructure
  • Nonmuscle Myosin Type IIA / chemistry*
  • Nonmuscle Myosin Type IIA / metabolism*
  • Nonmuscle Myosin Type IIA / ultrastructure
  • Nonmuscle Myosin Type IIB / chemistry*
  • Nonmuscle Myosin Type IIB / metabolism*
  • Nonmuscle Myosin Type IIB / ultrastructure
  • Protein Binding
  • Thermodynamics


  • Actins
  • Molecular Motor Proteins
  • Myosin Subfragments
  • Adenosine Diphosphate
  • Adenosine Triphosphate
  • Nonmuscle Myosin Type IIA
  • Nonmuscle Myosin Type IIB