Elastic lever-arm model for myosin V.
We present a mechanochemical model for myosin V, a two-headed processive motor protein. We derive the properties of a dimer from those of an individual head, which we model both with a four-state cycle (detached; attached with ADP.Pi; attached with ADP; and attached without nucleotide) and alternatively with a five-state cycle (where the powerstroke is not tightly coupled to the phosphate release). In each state the lever arm leaves the head at a different, but fixed, angle. The lever arm itself is described as an elastic rod. The chemical cycles of both heads are coordinated exclusively by the mechanical connection between the two lever arms. The model explains head coordination by showing that the lead head only binds to actin after the powerstroke in the trail head and that it only undergoes its powerstroke after the trail head unbinds from actin. Both models (four- and five-state) reproduce the observed hand-over-hand motion and fit the measured force-velocity relations. The main difference between the two models concerns the load dependence of the run length, which is much weaker in the five-state model. We show how systematic processivity measurement under varying conditions could be used to distinguish between both models and to determine the kinetic parameters.
Vilfan
Andrej
A
J. Stefan Institute, Ljubljana, Slovenia. andrej.vilfan@ijs.si
D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D055592:Biophysical Phenomena; D001703:Biophysics; D019281:Dimerization; D004548:Elasticity; D004734:Energy Metabolism; D066298:In Vitro Techniques; D007700:Kinetics; D008954:Models, Biological; D008958:Models, Molecular; D020409:Molecular Motor Proteins / Q000737:chemistry* / Q000378:metabolism*; D024701:Myosin Type V / Q000737:chemistry* / Q000378:metabolism*; D010710:Phosphates / Q000378:metabolism; D020836:Protein Structure, Quaternary; D013816:Thermodynamics
D020409:Molecular Motor Proteins; D010710:Phosphates; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D024701:Myosin Type V