Kinetics Study On The Processivity Of Myosin V

Myosin V,as one of the most common linear molecular motor,is a nanometer-sized machine that transforms chemical energy liberated by ATP hydrolysis into mechanical work.It involves in many intracellular transport processses such as organelle and mRNA and so on.Directional and processive movement of myosin V along actin filaments is essential for the fulfillment of its functions.Dwell-time distributuions are widely reported for myosin V based on the single-molecule biophysical experiments which showed that the dwell time distribution is nearly dual exponential form with coefficients closely related to the ATP and ADP concentration and the load.As well as they have significant effects on mean velocity and run length distributuion of myosin V.The existing theoretical research is still difficult to fully explain the experimental phenomena.Myosin V movement contains a profound chemical kinetics mechanism,so mechanochemical model is an effective method for studying the characteristics of its movement.Single-molecule biophysical experiments show that increasing the concentration of ATP decreases the dwell time and increases the mean velocity.Meanwhile the ADP release is the rate-limiting transition in the myosin-V mechanochemical cycle.Based on the above facts,the traditional polymorphic models are simplified and a three-state mechanochemical coupling model is developed in which the processes of ADP release and its inverse and ATP binding are regarded as the decisive factors.Compared with the traditional mechanical chemical coupling model,the model is simplified in the following aspects.1.In the statistical meaning,it is considered that the mechanical and chemical cycles of the two heads of myosin are relatively independent.2.The chemical cycle of myosin V is simplified to several steps including ATP binding and ADP binding and ADP release with ignoring Pi release.3.In the aspect of mechanics and chemical coupling mechanism,the complex conformational changes and their effects on the rate of chemical reaction aren't taken into account in myosin motion.The influence of external force on chemical reaction rate are considered.The traditional polymorphic model can calculate more accurate results.But due to considering so many the state transsitions and the chemical mechanical coupling,it is difficult to give an analytical solution for the processive motion of molecular motor.Compared with the most simple two-state model,the three-state model in this paper can separate the role of ATP and ADP in the ATP hydrolysis and then reflect the effects of ATP and ADP on the processivity of molecular motors.The three-state model makes up for the deficiency of the two state model.In this paper,according to a simplified mechanochemical coupling model,the processivity of myosin V is studied quantitatively.The effects of the ATP and ADP concentration and the load on the dwell time and the average velocity and the run length are investigated.The results are as follows:1.The analytical solutions of the dwell time distribution and the average velocity are obtained,and the quantitative relations between them and the ATP and ADP concentration and the load are defined.2.The joint probability distribution of the dwell time of myosin V is given and the analytical solution of the run length distribution is obtained.The theoretical results are in agreement with the experimental data,which proves that the simplified model proposed in this paper is reasonable and feasible.Our model may provide a new theoretical method for the study of myosin V.In this study it is also found that the ATP and ADP concentration ratio plays a decisive role for the dwell time and the average velocity,so the competition between ATP and ADP is an important factor in regulating movement characteristics of myosin V.