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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >An unlocking/relocking barrier in conformational fluctuations of villin headpiece subdomain
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An unlocking/relocking barrier in conformational fluctuations of villin headpiece subdomain

机译：villin头饰子域构象波动中的解锁/重新锁定屏障

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摘要

A reversible structural unlocking reaction, in which the close-packed van der Waals interactions break cooperatively, has been found for the villin headpiece subdomain (HP35) using triplet-triplet-energy transfer to monitor conformational fluctuations from equilibrium. Unlocking is associated with an unfavorable enthalpy change (ΔH~0 =35±4 kJ/mol) which is nearly compensated in free energy by the entropy change (ΔS~0 = 112 ± 20 J · mol~(-1) · K~(-1)). The unlocking reaction has a time constant of about 1 μs at 5 ℃ and is enthalpy-limited with an activation energy of 32 ± 1 kJ/mol and a large Arrhenius preexponential factor of A = 7.5 × 10~(11) s~(-1). In the unlocked state a fast local conformational fluctuation with a time constant of 170 ns and a low activation barrier of 17 ±1 kJ/mol leads to unfolding of the C-terminal helix and to its undocking from the core. On a much slower time scale, global unfolding occurs from the unlocked state. These results suggest that native protein structures are locked into conformations with low amplitude motions. Large scale motions and global unfolding require an initial structural unlocking step leading to a state with properties of a dry molten globule. The experiments additionally yielded information on the dynamics of loop formation between different positions in unfolded HP35. Comparison of the results with dynamics in unstructured model peptides indicates slightly decelerated kinetics of local loop formation in the C-terminal region which points at residual, nonrandom structure. Dynamics of long-range loop formation, in contrast, are not influenced by residual structure, which argues against unfolded state properties as molecular origin for ultrafast folding of HP35.
机译：使用三重态-三重态能量转移来监测构象波动（来自平衡状态），在维尔林头饰子域（HP35）中发现了紧密堆积的范德华相互作用协同破坏的可逆结构解锁反应。解锁与不利的焓变（ΔH〜0 = 35±4 kJ / mol）相关，该焓变几乎可以通过熵变（ΔS〜0 = 112±20 J·mol〜（-1）·K〜 （-1））。解锁反应在5℃时的时间常数约为1μs，并且受焓限制，其活化能为32±1 kJ / mol，Arrhenius预指数因数大，为A = 7.5×10〜（11）s〜（- 1）。在未锁定状态下，时间常数为170 ns的快速局部构象波动和17±1 kJ / mol的低激活势垒会导致C末端螺旋的展开以及其与核心的对接。在非常慢的时间尺度上，全局展开是从解锁状态开始的。这些结果表明，天然蛋白结构被锁定为低振幅运动的构象。大规模运动和整体展开需要初始的结构解锁步骤，从而导致具有干燥熔融小球特性的状态。实验还获得了有关展开的HP35中不同位置之间环形成动力学的信息。将结果与非结构化模型肽中的动力学进行比较表明，C端区域中局部环形成的动力学略有减速，这指向了残留的非随机结构。相比之下，远距离环形成的动力学不受残留结构的影响，而残留结构则反对未折叠的状态特性作为HP35超快折叠的分子起源。

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