Universität zu Köln

Zanotti, Andrea, Coelho, Joao P. L., Kaylani, Dinah, Singh, Gurdeep, Tauber, Marina, Hitzenberger, Manuel ORCID: 0000-0001-9726-2370, Avci, Donem, Zacharias, Martin, Russell, Robert B., Lemberg, Marius K. and Feige, Matthias J. (2022). The human signal peptidase complex acts as a quality control enzyme for membrane proteins. Science, 378 (6623). S. 996 - 1001. WASHINGTON: AMER ASSOC ADVANCEMENT SCIENCE. ISSN 1095-9203

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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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Zanotti, Andrea UNSPECIFIED UNSPECIFIED UNSPECIFIED Coelho, Joao P. L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kaylani, Dinah UNSPECIFIED UNSPECIFIED UNSPECIFIED Singh, Gurdeep UNSPECIFIED UNSPECIFIED UNSPECIFIED Tauber, Marina UNSPECIFIED UNSPECIFIED UNSPECIFIED Hitzenberger, Manuel UNSPECIFIED orcid.org/0000-0001-9726-2370 UNSPECIFIED Avci, Donem UNSPECIFIED UNSPECIFIED UNSPECIFIED Zacharias, Martin UNSPECIFIED UNSPECIFIED UNSPECIFIED Russell, Robert B. UNSPECIFIED UNSPECIFIED UNSPECIFIED Lemberg, Marius K. UNSPECIFIED UNSPECIFIED UNSPECIFIED Feige, Matthias J. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-676117
DOI:	10.1126/science.abo5672
Journal or Publication Title:	Science
Volume:	378
Number:	6623
Page Range:	S. 996 - 1001
Date:	2022
Publisher:	AMER ASSOC ADVANCEMENT SCIENCE
Place of Publication:	WASHINGTON
ISSN:	1095-9203
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language POSTTRANSLATIONAL N-GLYCOSYLATION; ER-ASSOCIATED DEGRADATION; PATHWAY; IRHOM2 Multiple languages Multidisciplinary Sciences Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/67611