Dynamic polymorphism of Ras observed by single molecule FRET is the basis for molecular recognition

Dynamic polymorphism of Ras observed by single molecule FRET is the basis for molecular recognition
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DOI:
10.1016/j.bbrc.2006.03.031
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发表时间:
2006-05-12
影响因子:
3.1
通讯作者:
Yanagida, T
Yanagida, T
中科院分区:
生物学4区
文献类型:
--
作者:
Arai, Y;Iwane, AH;Yanagida, T

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Ras 通过与各种效应器动态相互作用来调节信号转导通路功能。为了了解 Ras 功能的基础,在存在和不存在效应子的情况下,使用位于 Switch II 区域和 GTP 的探针之间的单分子荧光共振能量转移 (FRET) 来测量 Ras 的构象动力学。 GTP 结合 Ras 的 FRET 效率的时间轨迹表明,这种构象在多个状态之间自发变化。其中,低FRET状态被确定为非活动状态。涉及非活性构象状态的转变发生在几秒的时间范围内。相比之下,多个活跃的高 FRET 构象状态之间最有可能发生的波动持续了大约 30 秒,但在与效应器结合后收敛到特定的构象状态。因此,Ras 构象自发波动,易于与各种效应子相互作用。 (c) 2006 Elsevier Inc. 保留所有权利。
Ras regulates signal transduction pathway function by dynamically interacting with various effectors. TO understand the basis for Ras function, its conformational dynamics were measured in the absence and presence of effectors using single molecule fluorescence resonance energy transfer (FRET) between probes located on the Switch II region and GTP. The time trajectories of FRET efficiency from GTP-bound Ras showed that this conformation spontaneously varies among Multiple states. Among them, a low FRET state was identified as an inactive state. The transition involving the inactive conformational state occurred in the time range of seconds. In contrast, fluctuation occurring most probably between multiple active high FRET conformational states lasted similar to 30 ins but converged to a specific conformational state upon binding to an effector. Thus, Ras conformation spontaneously fluctuates to readily interact with various effectors. (c) 2006 Elsevier Inc. All rights reserved.