Federal Research Center "Fundamentals of Biotechnology", Russian Academy of Sciences, Moscow, 119071, Russia.
Biochemistry (Mosc). 2022 Jan;87(Suppl 1):S128-S19. doi: 10.1134/S0006297922140115.
The problem of linear polypeptide chain folding into a unique tertiary structure is one of the fundamental scientific challenges. The process of folding cannot be fully understood without its biological context, especially for big multidomain and multisubunit proteins. The principal features of biosynthetic folding are co-translational folding of growing nascent polypeptide chains and involvement of molecular chaperones in the process. The review summarizes available data on the early events of nascent chain folding, as well as on later advanced steps, including formation of elements of native structure. The relationship between the non-uniformity of translation rate and folding of the growing polypeptide is discussed. The results of studies on the effect of biosynthetic folding features on the parameters of folding as a physical process, its kinetics and mechanisms, are presented. Current understanding and hypotheses on the relationship of biosynthetic folding with the fundamental physical parameters and current views on polypeptide folding in the context of energy landscapes are discussed.
线性多肽链折叠成独特的三级结构的问题是一个基本的科学挑战。如果没有其生物背景，折叠过程就无法完全被理解，尤其是对于大的多域和多亚基蛋白质。生物合成折叠的主要特征是生长中的新生多肽链的共翻译折叠以及分子伴侣在该过程中的参与。该综述总结了关于新生链折叠的早期事件以及后来的高级步骤的现有数据，包括形成天然结构元件。讨论了翻译速率的不均匀性与生长多肽折叠之间的关系。介绍了关于生物合成折叠特征对折叠作为物理过程的参数、动力学和机制的影响的研究结果。讨论了当前对生物合成折叠与基本物理参数的关系的理解和假设，以及在能量景观背景下对多肽折叠的当前观点。
