Early events, kinetic intermediates and the mechanism of protein folding in cytochrome C.
Early events, kinetic intermediates and the mechanism of protein folding in cytochrome C.
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DOI：
10.3390/ijms10041476
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发表时间：
2009-04-01
影响因子：
5.6
通讯作者：
Kliger DS
中科院分区：
文献类型：
--
作者：
Goldbeck RA;Chen E;Kliger DS
本文综述了细胞色素c折叠过程中早期事件的动力学研究，重点是亚毫秒时间尺度上折叠中间体的证据。时间分辨吸收光谱、圆二色性、磁性圆二色性、荧光能量和电子转移、小角X射线散射和酰胺氢交换研究在t ≤ 1 ms的时间尺度上揭示了细胞色素c折叠的图像，其始于展开链的~ 1 μs构象扩散动力学。未折叠链的部分种群在1 - 100 μs的时间尺度上崩溃为包含一些类似天然二级结构的紧凑中间IC。虽然IC作为离散折叠中间体的存在和性质仍然存在争议，但有广泛的高时间分辨率动力学证据表明IC作为真正的中间体快速形成，即，通过离散自由能垒与未折叠状态分开的亚稳态。最终折叠到天然状态发生在毫秒和更长的时间尺度上，这取决于动力学陷阱的存在，如血红素错连接和脯氨酸错异构化。在平衡熔融球模型中观察到的高折叠速率表明IC可能是一种生产性折叠中间体。然而，这是否是通往与毫秒时间尺度折叠到天然状态相关的高自由能势垒的途径上的强制性步骤，仍有待确定。
Kinetic studies of the early events in cytochrome c folding are reviewed with a focus on the evidence for folding intermediates on the submillisecond timescale. Evidence from time-resolved absorption, circular dichroism, magnetic circular dichroism, fluorescence energy and electron transfer, small-angle X-ray scattering and amide hydrogen exchange studies on the t ≤ 1 ms timescale reveals a picture of cytochrome c folding that starts with the ~ 1-μs conformational diffusion dynamics of the unfolded chains. A fractional population of the unfolded chains collapses on the 1 – 100 μs timescale to a compact intermediate IC containing some native-like secondary structure. Although the existence and nature of IC as a discrete folding intermediate remains controversial, there is extensive high time-resolution kinetic evidence for the rapid formation of IC as a true intermediate, i.e., a metastable state separated from the unfolded state by a discrete free energy barrier. Final folding to the native state takes place on millisecond and longer timescales, depending on the presence of kinetic traps such as heme misligation and proline mis-isomerization. The high folding rates observed in equilibrium molten globule models suggest that IC may be a productive folding intermediate. Whether it is an obligatory step on the pathway to the high free energy barrier associated with millisecond timescale folding to the native state, however, remains to be determined.
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DOI：
10.1073/pnas.94.5.1779
发表时间：
1997-03-04
影响因子：
11.1
作者：
Chan, CK;Hu, Y;Hofrichter, J
通讯作者：
Hofrichter, J
DOI：
10.1038/nsb1296-1019
发表时间：
1996-12-01
期刊：
NATURE STRUCTURAL BIOLOGY
影响因子：
--
作者：
Colon, W;Roder, H
通讯作者：
Roder, H
影响因子：
5.6
作者：
Hagen, SJ;Eaton, WA
通讯作者：
Eaton, WA
影响因子：
2.9
作者：
Chen, EF;Wood, MJ;Kliger, DS
通讯作者：
Kliger, DS
DOI：
10.1073/pnas.96.17.9597
发表时间：
1999-08-17
影响因子：
11.1
作者：
Bieri, O;Wirz, J;Kiefhaber, T
通讯作者：
Kiefhaber, T