Mechanochemical Model of the Power Stroke of the Single-Headed Motor Protein KIF1A.

During the process of ATP binding to an apo-kinesin microtubule (MT), the kinesin core rotates on the MT, and the neck linker (NL) of the kinesin undergoes an undocked to docked transition. This has been suggested to be a power stroke of kinesin, on the basis of the structural analysis. Here, we developed a mesoscopic structure-based model and studied the power stroke of KIF1A. We quantified the underlying free energy landscape and showed the emergence of several states for the power stroke of KIF1A: UB-UR-UD (unbound, unrotating, undock), B-IR-UD (bound, initial rotating, undock), B-PR-UD (bound, partial rotating, undock), and B-R-D (bound, rotating, dock). We found that ATP binding triggered conformational fluctuations of key elements. We also explored the conformational change of key structural elements during the rotation of KIF1A and docking of the NL. In addition, we semiquantitatively and qualitatively estimated the free energy released by the ATP binding, and how much of this remains for the docking of the NL during the power stroke process at different temperatures. Finally, based on results from the thermodynamics landscape and conformational change of structural key elements, we proposed a mechanochemical model of the power stroke of KIF1A.