Department of Medical Biochemistry and Molecular Biology, Saarland University, 66421 Homburg, Germany.
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 7610001, Israel.
Int J Mol Sci. 2021 Dec 23;23(1):143. doi: 10.3390/ijms23010143.
Looking at the variety of the thousands of different polypeptides that have been focused on in the research on the endoplasmic reticulum from the last five decades taught us one humble lesson: no one size fits all. Cells use an impressive array of components to enable the safe transport of protein cargo from the cytosolic ribosomes to the endoplasmic reticulum. Safety during the transit is warranted by the interplay of cytosolic chaperones, membrane receptors, and protein translocases that together form functional networks and serve as protein targeting and translocation routes. While two targeting routes to the endoplasmic reticulum, SRP (signal recognition particle) and GET (guided entry of tail-anchored proteins), prefer targeting determinants at the N- and C-terminus of the cargo polypeptide, respectively, the recently discovered SND (SRP-independent) route seems to preferentially cater for cargos with non-generic targeting signals that are less hydrophobic or more distant from the termini. With an emphasis on targeting routes and protein translocases, we will discuss those functional networks that drive efficient protein topogenesis and shed light on their redundant and dynamic nature in health and disease.
纵观过去五十年内质网研究中聚焦的数千种不同多肽，我们得到了一个谦逊的教训：没有一种方法适用于所有情况。细胞使用令人印象深刻的一系列组件来实现从胞质核糖体到内质网的蛋白质货物的安全运输。胞质伴侣、膜受体和蛋白移位酶的相互作用保证了运输过程中的安全性，它们共同形成功能网络，并作为蛋白质靶向和易位途径。虽然有两种靶向内质网的途径，即 SRP（信号识别颗粒）和 GET（尾部锚定蛋白的引导进入），分别优先靶向货物多肽的 N 端和 C 端的靶向决定因素，但最近发现的 SND（非 SRP 依赖）途径似乎更优先针对靶向信号不常见、疏水性较低或距离末端较远的货物。本文重点介绍靶向途径和蛋白移位酶，讨论那些驱动有效蛋白质拓扑发生的功能网络，并阐明它们在健康和疾病中的冗余和动态性质。
