Abstract
A chemomechanical-network model for myosin V is presented on the basis of both the nucleotide-dependent binding affinity of the head to an actin filament (AF) and asymmetries and similarity relations among the chemical transitions due to an intramolecular strain of the leading and trailing heads. The model allows for branched chemomechanical cycles and takes into account not only two different force-generating mechanical transitions between states wherein the leading head is strongly bound and the trailing head is weakly bound to the AF but also load-induced mechanical-slip transitions between states in which both heads are strongly bound. The latter is supported by the fact that ATP-independent high-speed backward stepping has been observed for myosin V, although such motility has never been for kinesin. The network model appears as follows: (1) the high chemomechanical-coupling ratio between forward step and ATP hydrolysis is achieved even at low ATP concentrations by the dual mechanical transitions; (2) the forward stepping at high ATP concentrations is explained by the front head-gating mechanism wherein the power stroke is triggered by the inorganic-phosphate (Pi) release from the leading head; (3) the ATP-binding or hydrolyzed ADP.Pi-binding leading head produces a stable binding to the AF, especially against backward loading.
Highlights
In this study, we presented a systematic modelling of molecular-motor myosin V on the basis of a chemomechanical network theory[22,24]
We examined the validity of the manually determined parameters by applying to both ATP-concentration dependences of the motor velocity under constant loads [Fig. 2a,b] and ATP- and ADP-concentration dependences of motor velocity without external loading [Fig. 3a,d]
It is because, the molecular origin of the asymmetries and similarity relations newly introduced for myosin V in this study is basically interpreted by the intramolecular strain of the leading and trailing heads, in other words, the difference in the catalytic-domain conformations between of the leading and trailing heads with the post-recovery-stroke and pre-recovery-stroke conformations, respectively
Summary
The dynamics of a molecular motor can be described by a continuous-time Markov process. The probability Pi(t) of finding the molecular motor in state i at time t is governed by the following continuous-time master equations: d dt Pi(t) = − ∑ΔJij(t), j (1). ΔJij(t) = Jij(t) − Jji(t) = Pi(t)ωij − Pj(t)ωji, (2). Where ωij is a transition rate from state i to state j, i.e. the number of transitions from i to j per unit time, Jij(t) and ΔJij(t); the local flux and local excess flux due to the transition from state i to state j. The transition rate, ωij, depends on both the external load parallel to the actin filament, F, and the molar concentrations [X], where X denotes the molecular species ATP, ADP, or Pi (inorganic phosphate). The transition rates can be given by ωij = ωi0j Φij(F), (3)
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