Over five decades of research have yielded a large body of information on how purified proteins attain their native state when refolded in the test tube, starting from a chemically or thermally denatured state. Nevertheless, we still know little about how proteins fold and unfold in their natural biological habitat: the living cell. Indeed, a variety of cellular components, including molecular chaperones, the ribosome, and crowding of the intracellular medium, modulate folding mechanisms in physiologically relevant environments. This review focuses on the current state of knowledge in protein folding in the cell with emphasis on the early stage of a protein's life, as the nascent polypeptide traverses and emerges from the ribosomal tunnel. Given the vectorial nature of ribosome-assisted translation, the transient degree of chain elongation becomes a relevant variable expected to affect nascent protein foldability, aggregation propensity and extent of interaction with chaperones and the ribosome.

中文翻译：

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蛋白质在出口隧道处折叠。


超过五十年的研究已经获得了大量有关纯化蛋白质在试管中重新折叠时如何从化学或热变性状态开始达到其天然状态的信息。尽管如此，我们对蛋白质如何在其自然生物栖息地：活细胞中折叠和展开仍然知之甚少。事实上，多种细胞成分，包括分子伴侣、核糖体和细胞内介质的拥挤，在生理相关环境中调节折叠机制。本综述重点关注细胞中蛋白质折叠的当前知识状况，重点关注蛋白质生命的早期阶段，即新生多肽穿过核糖体隧道并从核糖体隧道中出现。考虑到核糖体辅助翻译的矢量性质，链伸长的瞬时程度成为一个相关变量，预计会影响新生蛋白质的折叠性、聚集倾向以及与伴侣和核糖体相互作用的程度。