Posttranslational translocon architecture About a third of proteins are transported into endoplasmic reticulum by the universally conserved Sec61 protein-conducting channel. Itskanov and Park determined a cryo–electron microscopy structure of the Sec complex from yeast, which mediates posttranslational translocation of many secretory proteins across the endoplasmic reticulum membrane. The study reveals how Sec63 activates the Sec61 channel for substrate polypeptide insertion. The structure also explains the mutually exclusive binding of Sec63 and the ribosome to the channel. Science, this issue p. 84 Structural analysis elucidates the mechanism of eukaryotic posttranslational protein translocation. The Sec61 protein-conducting channel mediates transport of many proteins, such as secretory proteins, across the endoplasmic reticulum (ER) membrane during or after translation. Posttranslational transport is enabled by two additional membrane proteins associated with the channel, Sec63 and Sec62, but its mechanism is poorly understood. We determined a structure of the Sec complex (Sec61-Sec63-Sec71-Sec72) from Saccharomyces cerevisiae by cryo–electron microscopy (cryo-EM). The structure shows that Sec63 tightly associates with Sec61 through interactions in cytosolic, transmembrane, and ER-luminal domains, prying open Sec61’s lateral gate and translocation pore and thus activating the channel for substrate engagement. Furthermore, Sec63 optimally positions binding sites for cytosolic and luminal chaperones in the complex to enable efficient polypeptide translocation. Our study provides mechanistic insights into eukaryotic posttranslational protein translocation.

中文翻译：

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来自酵母的翻译后 Sec 蛋白-易位通道复合物的结构

翻译后转位子结构大约三分之一的蛋白质通过普遍保守的 Sec61 蛋白质传导通道转运到内质网中。Itskanov 和 Park 确定了酵母 Sec 复合物的冷冻电子显微镜结构，它介导了许多分泌蛋白跨内质网膜的翻译后易位。该研究揭示了 Sec63 如何激活 Sec61 通道以插入底物多肽。该结构还解释了 Sec63 和核糖体与通道的互斥结合。科学，这个问题 p。84 结构分析阐明了真核生物翻译后蛋白质易位的机制。Sec61 蛋白传导通道介导许多蛋白的转运，例如分泌蛋白、在翻译过程中或翻译后穿过内质网 (ER) 膜。翻译后转运是由两个与通道相关的额外膜蛋白 Sec63 和 Sec62 启用的，但其机制知之甚少。我们通过冷冻电子显微镜 (cryo-EM) 确定了来自酿酒酵母的 Sec 复合物 (Sec61-Sec63-Sec71-Sec72) 的结构。该结构表明，Sec63 通过胞质、跨膜和内质网腔域中的相互作用与 Sec61 紧密结合，撬开 Sec61 的侧门和易位孔，从而激活底物接合的通道。此外，Sec63 优化定位复合物中胞质和管腔伴侣的结合位点，以实现有效的多肽易位。