Recent insights into the relative timing of myosin's powerstroke and release of phosphate.
Recent insights into the relative timing of myosin's powerstroke and release of phosphate.
复制标题
肌球蛋白的动力冲程和磷酸盐释放的相对时间的最新见解。
DOI：
10.1002/cm.21695
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发表时间：
2021-09
期刊：
影响因子：
--
通讯作者：
中科院分区：
文献类型：
--
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肌球蛋白是一种运动酶，它将ATP中的化学能转化为机械功，以驱动无数的细胞内过程，从肌肉收缩到囊泡运输。能量转换的关键步骤是产生力量的动力冲程，以及从核苷酸结合位点释放磷酸盐（Pi）。这两个事件都在与肌动蛋白结合后迅速发生，使得很难确定哪个事件先发生。早期的研究表明，这些事件同时发生;然而，最近的研究结果表明，它们是以不同速率发生的独立和不同的事件。在ATP酶循环的中间状态捕获的肌球蛋白的高分辨率晶体结构表明，当Pi处于活性位点时，它可以防止发生动力中风，从而导致Pi释放先于动力中风的假设。然而，功能测定的进展，使亚毫秒的时间和纳米空间分辨率，挑战这一假设。例如，基于Föster共振能量转移（FRET）的测定以及单分子激光陷阱测定表明相反;动力中风发生在Pi从肌球蛋白的活性位点释放之前。这篇综述提供了一些历史背景，然后强调了最近的报告，揭示了令人兴奋的新的洞察力，这一基本机制的能量转导的这种原型马达酶。
Myosin is a motor enzyme that converts the chemical energy in ATP into mechanical work to drive a myriad of intracellular processes, from muscle contraction to vesicular transport. Key steps in the transduction of energy are the force-generating powerstroke, and the release of phosphate (Pi) from the nucleotide-binding site. Both events occur rapidly after binding to actin, making it difficult to determine which event occurs first. Early efforts suggested that these events occur simultaneously; however, recent findings indicate that they are separate and distinct events that occur at different rates. High-resolution crystal structures of myosin captured in intermediate states of the ATPase cycle suggest that when Pi is in the active site it prevents the powerstroke from occurring, leading to the hypothesis that Pi-release precedes the powerstroke. However, advances in functional assays, enabling sub-millisecond temporal and nanometer spatial resolution, are challenging this hypothesis. For example, Föster Resonance Energy Transfer (FRET) based assays, as well as single molecule laser trap assays, suggest the opposite; that the powerstroke occurs prior to the release of Pi from myosin’s active site. This review provides some historical context and then highlights recent reports that reveal exciting new insight into this fundamental mechanism of energy transduction by this prototypical motor enzyme.
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影响因子：
2.9
作者：
LYMN, RW;TAYLOR, EW
通讯作者：
TAYLOR, EW
DOI：
10.1073/pnas.96.24.13726
发表时间：
1999-11-23
影响因子：
11.1
作者：
De La Cruz, EM;Wells, AL;Sweeney, HL
通讯作者：
Sweeney, HL
影响因子：
64.5
作者：
Dominguez, R;Freyzon, Y;Cohen, C
通讯作者：
Cohen, C
影响因子：
64.8
作者：
FINER, JT;SIMMONS, RM;SPUDICH, JA
通讯作者：
SPUDICH, JA
影响因子：
56.9
作者：
EISENBERG, E;HILL, TL
通讯作者：
HILL, TL