The human signal peptidase complex acts as a quality control enzyme for membrane proteins

Autor:	Andrea Zanotti, João P. L. Coelho, Dinah Kaylani, Gurdeep Singh, Marina Tauber, Manuel Hitzenberger, Dönem Avci, Martin Zacharias, Robert B. Russell, Marius K. Lemberg, Matthias J. Feige
Rok vydání:	2022
Předmět:	Multidisciplinary Proteome Serine Endopeptidases Proteolysis Humans Membrane Proteins Endoplasmic Reticulum-Associated Degradation Endoplasmic Reticulum
Zdroj:	Science (New York, N.Y.). 378(6623)
ISSN:	1095-9203
Popis:	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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ebb1342bb70c0289f2e44fda26fe4eca https://pubmed.ncbi.nlm.nih.gov/36454823 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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