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.

中文翻译：

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人信号肽酶复合物作为膜蛋白的质量控制酶

细胞需要检测和降解有缺陷的膜蛋白以维持体内平衡。在这项研究中，我们确定了人类信号肽酶复合物 (SPC) 以前未知的功能——去除内质网 (ER) 信号肽的酶——作为膜蛋白质量控制因素。我们表明，SPC 会在其他隐藏的切割位点切割无法正确折叠或组装成其天然复合物的膜蛋白，我们的研究表明，这些蛋白在人类膜蛋白质组中非常丰富。这种易位后切割与 ER 相关的降解协同作用以维持膜蛋白稳态并有助于细胞健康。因此，隐蔽的 SPC 切割位点作为预定的断裂点，当暴露时，有助于靶向错误折叠或多余的蛋白质进行降解，