School of Material Science and Engineering, Central South University of Forestry and Technology, Changsha, China.
Key Laboratory of Soft Matter Physics, Institute of Physics, Chinese Academy of Sciences, Beijing, China.
Proteins. 2020 Apr;88(4):545-557. doi: 10.1002/prot.25833. Epub 2019 Oct 13.
Kinesin dimer walks processively along a microtubule (MT) protofilament in a hand-over-hand manner, transiting alternately between one-head-bound (1HB) and two-heads-bound (2HB) states. In 1HB state, one head bound by adenosine diphosphate (ADP) is detached from MT and the other head is bound to MT. Here, using all-atom molecular dynamics simulations we determined the position and orientation of the detached ADP-head relative to the MT-bound head in 1HB state. We showed that in 1HB state when the MT-bound head is in ADP or nucleotide-free state, with its neck linker being undocked, the detached ADP-head and the MT-bound head have the high binding energy, and after adenosine triphosphate (ATP) binds to the MT-bound head, with its neck linker being docked, the binding energy between the two heads is reduced greatly. These results reveal how the kinesin dimer retains 1HB state before ATP binding and how the dimer transits from 1HB to 2HB state after ATP binding. Key residues involved in the head-head interaction in 1HB state were identified.
驱动蛋白二聚体以节节相连的方式沿微管（MT）原丝进行行进性运动，交替地在单头结合（1HB）和双头结合（2HB）状态之间转换。在 1HB 状态下，一个结合二磷酸腺苷（ADP）的头部从 MT 上脱离，另一个头部结合 MT。在这里，我们使用全原子分子动力学模拟确定了 1HB 状态下脱离的 ADP 头部相对于 MT 结合头部的位置和取向。我们表明，在 1HB 状态下，当 MT 结合头部处于 ADP 或无核苷酸状态，其颈环脱钩时，脱离的 ADP 头部和 MT 结合头部具有高结合能，并且在三磷酸腺苷（ATP）结合 MT 结合头部后，其颈环对接，两个头部之间的结合能大大降低。这些结果揭示了驱动蛋白二聚体在结合 ATP 之前如何保持 1HB 状态，以及二聚体在结合 ATP 后如何从 1HB 状态过渡到 2HB 状态。确定了 1HB 状态下头对头相互作用涉及的关键残基。
