Atomistic analysis of ATP hydrolysis effect on a dynein walking mechanism

Dynein is a microtubule motor protein that is highly involved in cell motility. Although its atomic structure was recently reported, it has been believed that dynein, like other motor proteins, generates a large swing motion powered by ATP hydrolysis. In this paper, we have analyzed ATP hydrolysis effect on the walking mechanism of dynein at the atomic level using a C a coarse-grained elastic network model. Normal mode analysis (NMA) revealed that the detachment of the linker from the head of dynein, which is triggered by ATP hydrolysis, facilitates the main swing motion of dynein in two ways: allowing the bending motion as an extra degree-of-freedom (topologically) and lowering the energy barrier between the closed and open forms (energetically). This large conformational transition pathway is successfully generated by Elastic network interpolation (ENI). Comparison between the ENI pathway and the NMA results clearly elucidates the role of ATP hydrolysis in motor proteins as well as the swing motion of dynein in atomic detail.