All‐atom molecular dynamics simulations reveal how kinesin transits from one‐head‐bound to two‐heads‐bound state

Xiao-Xuan Shi, Si-Kao Guo, Pengye Wang, Hong Chen, P. Xie
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引用次数: 16

Abstract

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.
全原子分子动力学模拟揭示了动力学蛋白如何从一个头结合状态过渡到两个头结合状态
动力学蛋白二聚体以手-手的方式沿着微管(MT)原丝行进,在单头结合(1HB)和双头结合(2HB)状态之间交替过渡。在1HB状态下,与二磷酸腺苷(ADP)结合的一个头部与MT分离,另一个头部与MT结合。在这里,使用全原子分子动力学模拟,我们确定了与1HB状态下与MT结合的头部相比,分离的ADP头部的位置和方向。我们发现,在1HB状态下,当MT -结合头处于ADP或核苷酸无状态时,其颈连接体断开,分离的ADP -头与MT -结合头具有较高的结合能,三磷酸腺苷(ATP)与MT -结合头结合后,其颈连接体断开,两个头之间的结合能大大降低。这些结果揭示了二聚体在ATP结合前如何保持1HB状态,以及二聚体在ATP结合后如何从1HB状态转变为2HB状态。鉴定了1HB状态下参与头-头相互作用的关键残基。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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