| Regional Biophysics Meeting 2005, March 16-20, Zreče, Slovenia | [ProtBiophys] |
Myosin V is a motor protein which moves processively along actin filaments. It consists of two heads, similar to skeletal muscle myosin, but with longer lever arms which allow it to take steps of about 35nm length. We present a mechanochemical model to describe the coordinated hand-over-hand motion of a myosin V molecule. As a basis we use a 4- or 5- state model for an individual head, which is connected to a lever arm described as an elastic rod. In each state the lever arm emerges from the head at a different, fixed angle. The ends of the lever arms from both heads are connected together and to the external load by a flexible joint, and this is the only mechanism of communication between them. Based on these assumptions we derive the properties of a dimer from those of an individual head. The model is able to reproduce the coordinated hand-over-hand motion with a step size between 11 and 15 actin subunits. We show on the basis of mechanical considerations that the lead head cannot undergo its power stroke before the trail head detaches. Another interesting property of the model is that transitions between states with both heads bound (notably ADP release) show almost no load dependence - which explains the flat force-velocity curve at low loads. Depending on whether the phosphate release occurs before (5-state model) or during the power stroke (4-state model), we obtain two different scenarios, which both reproduce the sigmoidal force-velocity curves, but the 5-state model predicts a more abrupt drop in velocity near the stall force, a more uniform dissociation rate as a function of load and the ability of the motor to step backwards at super-stall forces. These properties are all in agreement with recent experiments and favor the scenario with immediate Pi release. We also show how measurements of run length as a function of force and nucleotide concentrations could be used to determine the remaining unknown kinetic rates.
Email: andrej.vilfan@ijs.si
Address: Jamova 39, 1000 Ljubljana, Slovenia