The human signal peptidase complex acts as a quality control enzyme for membrane proteins.
Science
; 378(6623): 996-1000, 2022 12 02.
Article
en En
| MEDLINE
| ID: mdl-36454823
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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Serina Endopeptidasas
/
Retículo Endoplásmico
/
Degradación Asociada con el Retículo Endoplásmico
/
Proteínas de la Membrana
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Science
Año:
2022
Tipo del documento:
Article
País de afiliación:
Alemania