研究人员确定了人类信号肽酶复合体（SPC），一个去除内质网（ER）信号肽的酶，作为膜蛋白质量控制因子的一个以前未知的功能。结果表明，SPC在其他隐藏的切割位点切割那些不能正确折叠或组装成其本地复合物的膜蛋白，研究结果显示，这些蛋白在人类膜蛋白组中非常丰富。这种翻译后的切割与ER相关的降解协同作用，维持膜蛋白的平衡，并有助于细胞的健康。因此，隐蔽的SPC切割位点作为预定的断裂点，一旦暴露，有助于将折叠错误或过剩的蛋白质作为靶标进行降解，从而维持健康的膜蛋白质组。
据悉，细胞需要检测和降解有问题的膜蛋白以维持平衡。
附：英文原文
Title: The human signal peptidase complex acts as a quality control enzyme for membrane proteins
Author: Andrea Zanotti, Joo P. L. Coelho, Dinah Kaylani, Gurdeep Singh, Marina Tauber, Manuel Hitzenberger, Dnem Avci, Martin Zacharias, Robert B. Russell, Marius K. Lemberg, Matthias J. Feige
Issue&Volume: 2022-12-02
Abstract: Cells need to detect and degrade faulty membrane proteins to maintain homeostasis. In this study, we identify a previously unknown function of the human signal peptidase complex (SPC)—the enzyme that removes endoplasmic reticulum (ER) signal peptides—as a membrane protein quality control factor. We show that the SPC cleaves membrane proteins that fail to correctly fold or assemble into their native complexes at otherwise hidden cleavage sites, which our study reveals to be abundant in the human membrane proteome. This posttranslocational cleavage synergizes with ER-associated degradation to sustain membrane protein homeostasis and contributes to cellular fitness. Cryptic SPC cleavage sites thus serve as predetermined breaking points that, when exposed, help to target misfolded or surplus proteins for degradation, thereby maintaining a healthy membrane proteome.
DOI: abo5672
Source: https://www.science.org/doi/10.1126/science.abo5672