Unification of the folding mechanisms of non-two-state and two-state proteins
Unification of the folding mechanisms of non-two-state and two-state proteins
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DOI：
10.1016/j.jmb.2004.04.015
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发表时间：
2004-06-11
影响因子：
5.6
通讯作者：
Kuwajima, K
中科院分区：
文献类型：
--
作者：
Kamagata, K;Arai, M;Kuwajima, K
我们收集了文献中报道的非双态和双态球状蛋白的动力学折叠数据，并研究了这些蛋白的折叠动力学与天然三维结构之间的关系。的中间和非两态文件夹的原生状态的形成的速率常数被发现是显着相关的蛋白质链长度和原生骨架拓扑结构，这是由绝对接触顺序和序列远的原生对。已知与天然骨架拓扑结构相关的双态文件夹的折叠速率显然与蛋白质链长度不显著相关。基于非双态和双态文件夹的折叠速率的比较，发现它们类似地依赖于反映原生骨干拓扑的参数。这表明非双态折叠和双态折叠背后的机制本质上是相同的。目前的结果使我们提出了一个统一的机制，蛋白质折叠，折叠发生在一个层次的方式，反映了层次的原生三维结构，体现在非两态折叠的情况下，积累的中间体。显然，双态折叠只是一个简化版本的分层折叠所造成的改变，在限速步骤的折叠或不稳定的中间体。(C)2004爱思唯尔有限公司保留所有权利。
We have collected the kinetic folding data for non-two-state and two-state globular proteins reported in the literature, and investigated the relationships between the folding kinetics and the native three-dimensional structure of these proteins. The rate constants of formation of both the intermediate and the native state of non-two-state folders were found to be significantly correlated with protein chain length and native backbone topology, which is represented by the absolute contact order and sequence-distant native pairs. The folding rate of two-state folders, which is known to be correlated with the native backbone topology, apparently does not correlate significantly with protein chain length. On the basis of a comparison of the folding rates of the non-two-state and two-state folders, it was found that they are similarly dependent on the parameters that reflect the native backbone topology. This suggests that the mechanisms behind non-two-state and two-state folding are essentially identical. The present results lead us to propose a unified mechanism of protein folding, in which folding occurs in a hierarchical manner, reflecting the hierarchy of the native three-dimensional structure, as embodied in the case of non-two-state folding with an accumulation of the intermediate. Apparently, two-state folding is merely a simplified version of hierarchical folding caused either by an alteration in the rate-limiting step of folding or by destabilization of the intermediate. (C) 2004 Elsevier Ltd. All rights reserved.