Cellular Protein Chemistry, Faculty of Science, Utrecht University, Utrecht, The Netherlands.
Annu Rev Biochem. 2011;80:71-99. doi: 10.1146/annurev-biochem-062209-093836.
Analysis of the human genome reveals that approximately a third of all open reading frames code for proteins that enter the endoplasmic reticulum (ER), demonstrating the importance of this organelle for global protein maturation. The path taken by a polypeptide through the secretory pathway starts with its translocation across or into the ER membrane. It then must fold and be modified correctly in the ER before being transported via the Golgi apparatus to the cell surface or another destination. Being physically segregated from the cytosol means that the ER lumen has a distinct folding environment. It contains much of the machinery for fulfilling the task of protein production, including complex pathways for folding, assembly, modification, quality control, and recycling. Importantly, the compartmentalization means that several modifications that do not occur in the cytosol, such as glycosylation and extensive disulfide bond formation, can occur to secreted proteins to enhance their stability before their exposure to the extracellular milieu. How these various machineries interact during the normal pathway of folding and protein secretion is the subject of this review.
人类基因组分析表明，大约三分之一的开放阅读框编码进入内质网 (ER) 的蛋白质，这表明这个细胞器对于全球蛋白质成熟的重要性。多肽通过分泌途径所走的路径始于其穿过或进入内质网膜的易位。然后，它必须在内质网中正确折叠和修饰，然后通过高尔基体运送到细胞表面或其他目的地。与细胞质物理分离意味着内质网腔具有独特的折叠环境。它包含了完成蛋白质生产任务的大部分机制，包括折叠、组装、修饰、质量控制和回收的复杂途径。重要的是，这种分隔意味着一些不在细胞质中发生的修饰，如糖基化和广泛的二硫键形成，可以发生在分泌蛋白上，以增强它们在暴露于细胞外环境之前的稳定性。这些各种机制在折叠和蛋白质分泌的正常途径中是如何相互作用的，这是本综述的主题。
