Generic maps of optimality reveal two chemomechanical coupling regimes for motor proteins: from F1-ATPase and kinesin to myosin and cytoplasmic dynein

Abstract

Many motor proteins achieve high efficiency for chemomechanical conversion, and single-molecule force-resisting experiments are a major tool to detect the chemomechanical coupling of efficient motors. Here, we introduce several quantitative relations that involve only parameters extracted from force-resisting experiments and offer new benchmarks beyond mere efficiency to judge the chemomechanical optimality or deficit of evolutionary remote motors on the same footing. The relations are verified by the experimental data from F-ATPase, kinesin-1, myosin V and cytoplasmic dynein, which are representative members of four motor protein families. A double-fitting procedure yields the chemomechanical parameters that can be cross-checked for consistency. Using the extracted parameters, two generic maps of chemomechanical optimality are constructed on which motors across families can be quantitatively compared. The maps reveal two chemomechanical coupling regimes, one conducive to high efficiency and high directionality, and the other advantageous to force generation. Surprisingly, an F rotor and a kinesin-1 walker belong to the first regime despite their obvious evolutionary gap, while myosin V and cytoplasmic dynein follow the second regime. This analysis also predicts the symmetries of directional biases and heat productions for the motors, which impose constraints on their chemomechanical coupling and are open to future experimental tests. The verified relations, six in total, present a unified fitting framework to analyze force-resisting experiments. The generic maps of optimality, to which many more motors can be added in future, provide a rigorous method for a systematic cross-family comparison of motors to expose their evolutionary connections and mechanistic similarities.

A high-fidelity light-powered nanomotor from a chemically fueled counterpart via site-specific optomechanical fuel control

“…4) is explained by the α and β biases produced by the fuel analogs. The direction signal recorded from the motility experiments is proportional to the motor's directional fidelity, 31–36 which quantifies the probability for a net forward step once the motor is activated by a light-responsive fuel analog. The directional fidelity for the bipedal motor is determined by the α and β biases as D = ( αβ − 1)/[( α + 1)( β + 1)] (Methods and materials).…”

“…The different energetics imply different concentration sensitivity for optically and chemically powered nanomotors. Nevertheless, this study shows that both types of motors can be analysed on the same footing using the concepts of stepping biases and directional fidelity, with the latter being equivalent of fuel efficiency 10 for chemical motors and operational efficiency for optical motors, and generally related to stall force 14 and efficiency 35 of any nanomotors. This study also identifies a new kinetic feature of azo-tethered DNA in inducing toehold-mediated strand displacement (TMSD), 48 which is a process widely used in DNA nanotechnology, and is responsible for fuel-analog-induced leg dissociation in this motor study.…”

“…The ordered product release and chemomechanical coupling are critical for channeling the chemical energy into driving for a motor's directional motion before the released chemical energy decays into heat. This is the major mechanistic origin of generally higher energy efficiency 34,35,46,47 for chemical molecular motors over internal combustion engines, though the latter are also powered by chemical fuels ultimately ( e.g. , gasoline molecules).…”

Extract Motive Energy from Single-Molecule Trajectories

“…Like eq 8, the relation ΔG min (D(f)) = ΔG min (D( f = 0)) − f•d 0 allows extraction of the stall force from trajectories at individual forces including zero force, namely, f stall = [ΔG min (D(f)) + f•d 0 ]/d 0 . However, this relation is found to be valid for F 1 -ATPase and kinesin-1 that are both efficient motors with tight chemomechanical coupling, but not for other motors (e.g., another biological translational molecular motor myosin V 46 ). This relation, and the ΔG Sd 0 − ΔG min (D) equivalence, certainly loses validity for the Brownian motor model studied in this study as it is a loosely coupled motor with D ≤ 1/2 43 and hence ΔG min (D) ≤ 2.2 k B T under zero force, but the corresponding ΔG Sd 0 can be much higher for this motor (see Figure 5b).…”

Mechanical transduction via a single soft polymer

“…This biasing capacity amounts to the maximum energy consumption associated with the forward leg binding. Then the total actual energy input to kinesin can be roughly estimated using a recent finding [67][68][69] that kinesin has almost equal energy consumption for the forward leg binding and the trailing leg dissociation. Thus the biasing capacity of the neck linkers implies that μ * is ∼16.6 k B T at best for kinesin.…”