The human signal peptidase complex acts as a quality control enzyme for membrane proteins.
Science
; 378(6623): 996-1000, 2022 12 02.
Article
em 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:
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Base de dados:
MEDLINE
Assunto principal:
Serina Endopeptidases
/
Retículo Endoplasmático
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Degradação Associada com o Retículo Endoplasmático
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Proteínas de Membrana
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article