The road less traveled in protein folding: evidence for multiple pathways

The road less traveled in protein folding: evidence for multiple pathways
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蛋白质折叠中少有人走的路:多种途径的证据

DOI:
10.1016/j.sbi.2020.10.012
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发表时间:
2021
影响因子:
6.8
通讯作者:
Lapidus, Lisa J
Lapidus, Lisa J
中科院分区:
生物学2区
文献类型:
--
作者:
Lapidus, Lisa J

文献摘要

相似文献

亮点蛋白质折叠领域越来越意识到多重折叠途径的可能性,但通过实验检测它们仍然是一个挑战。几种新的大体积和单分子技术已经描绘出多种蛋白质的多重路径。了解细胞环境如何改变这些路径可以更深入地了解体内折叠。需要新的计算技术来帮助实验人员描绘观察到的路径。20多年前推出的蛋白质折叠自由能景观理论意味着蛋白质有多种通往折叠构象的路径,且具有最低的折叠构象自由能源。尽管原则上已有所了解,但检测此类途径仍然非常困难。缺乏这样的观察结果主要是因为没有一种实验技术能够同时检测蛋白质的许多部分,并且具有观察路径差异所需的时间分辨率。然而,最近的技术发展以及多种实验探针和折叠提示的使用已经阐明了许多蛋白质中的多种折叠途径,而这些蛋白质以前都是用单一路径描述的。
HighlightsThe field of protein folding is increasingly aware of the possibility of multiple folding pathways but detecting them experimentally is still a challenge.Several new bulk and single molecule techniques have delineated multiple paths for a variety of proteins.Understanding how such paths are altered by a cellular environment gives greater insight into folding in vivo.New computational techniques are needed to help experimentalists delineate the observed paths.Free Energy Landscape theory of Protein Folding, introduced over 20 years ago, implies that a protein has many paths to the folded conformation with the lowest free energy. Despite the knowledge in principle, it has been remarkably hard to detect such pathways. The lack of such observations is primarily due to the fact that no one experimental technique can detect many parts of the protein simultaneously with the time resolution necessary to see such differences in paths. However, recent technical developments and employment of multiple experimental probes and folding prompts have illuminated multiple folding pathways in a number of proteins that had all previously been described with a single path.