Department of Physics, School of Science, the University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
School of Computational Sciences, Korea Institute for Advanced Study (KIAS), Seoul 02455, Korea.
Biomolecules. 2020 Mar 6;10(3):407. doi: 10.3390/biom10030407.
From experimental studies of protein folding, it is now clear that there are two types of folding behavior, i.e., two-state folding and non-two-state folding, and understanding the relationships between these apparently different folding behaviors is essential for fully elucidating the molecular mechanisms of protein folding. This article describes how the presence of the two types of folding behavior has been confirmed experimentally, and discusses the relationships between the two-state and the non-two-state folding reactions, on the basis of available data on the correlations of the folding rate constant with various structure-based properties, which are determined primarily by the backbone topology of proteins. Finally, a two-stage hierarchical model is proposed as a general mechanism of protein folding. In this model, protein 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 molten globule state as a folding intermediate. The two-state folding is thus merely a simplified version of the hierarchical folding caused either by an alteration in the rate-limiting step of folding or by destabilization of the intermediate.
从蛋白质折叠的实验研究中可以清楚地看出，存在两种折叠行为，即两态折叠和非两态折叠，理解这些明显不同的折叠行为之间的关系对于充分阐明蛋白质折叠的分子机制至关重要。本文描述了如何通过实验证实了这两种折叠行为的存在，并根据与折叠速率常数相关的各种基于结构的特性的相关性的现有数据，讨论了两态和非两态折叠反应之间的关系，这些相关性主要取决于蛋白质的骨架拓扑。最后，提出了一个两阶段层次模型作为蛋白质折叠的一般机制。在该模型中，蛋白质折叠以分层的方式发生，反映了天然三维结构的层次，在非两态折叠的情况下，这种情况表现为聚集的无规卷曲状态作为折叠中间体。因此，两态折叠只是由于折叠的限速步骤的改变或中间态的不稳定而导致的分层折叠的简化版本。
