折叠漏斗
蛋白质折叠
折叠(DSP实现)
化学
下坡褶皱
晶格蛋白
联系方式
熔球
亚稳态
能源景观
化学物理
成核
球状蛋白
结晶学
生物物理学
功率因数值分析
生物化学
生物
有机化学
工程类
电气工程
出处
期刊:Annual Review of Biophysics and Biomolecular Structure
[Annual Reviews]
日期:2000-06-01
卷期号:29 (1): 213-238
被引量:434
标识
DOI:10.1146/annurev.biophys.29.1.213
摘要
In order to solve the immensely difficult protein-folding problem, it will be necessary to characterize the barriers that slow folding and the intermediate structures that promote it. Although protein-folding intermediates are not accessible to the usual structural studies, hydrogen exchange (HX) methods have been able to detect and characterize intermediates in both kinetic and equilibrium modes--as transient kinetic folding intermediates on a subsecond time scale, as labile equilibrium molten globule intermediates under destabilizing conditions, and as infinitesimally populated intermediates in the high free-energy folding landscape under native conditions. Available results consistently indicate that protein-folding landscapes are dominated by a small number of discrete, metastable, native-like partially unfolded forms (PUFs). The PUFs appear to be produced, one from another, by the unfolding and refolding of the protein's intrinsically cooperative secondary structural elements, which can spontaneously create stepwise unfolding and refolding pathways. Kinetic experiments identify three kinds of barrier processes: (a) an initial intrinsic search-nucleation-collapse process that prepares the chain for intermediate formation by pinning it into a condensed coarsely native-like topology; (b) smaller search-dependent barriers that put the secondary structural units into place; and (c) optional error-dependent misfold-reorganization barriers that can cause slow folding, intermediate accumulation, and folding heterogeneity. These conclusions provide a coherent explanation for the grossly disparate folding behavior of different globular proteins in terms of distinct folding pathways.
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