Structural basis for regulation of apoptosis and autophagy by the BIRC6/SMAC complex.
Science
; 379(6637): 1117-1123, 2023 03 17.
Article
em En
| MEDLINE
| ID: mdl-36758105
ABSTRACT
Inhibitor of apoptosis proteins (IAPs) bind to pro-apoptotic proteases, keeping them inactive and preventing cell death. The atypical ubiquitin ligase BIRC6 is the only essential IAP, additionally functioning as a suppressor of autophagy. We performed a structure-function analysis of BIRC6 in complex with caspase-9, HTRA2, SMAC, and LC3B, which are critical apoptosis and autophagy proteins. Cryo-electron microscopy structures showed that BIRC6 forms a megadalton crescent shape that arcs around a spacious cavity containing receptor sites for client proteins. Multivalent binding of SMAC obstructs client binding, impeding ubiquitination of both autophagy and apoptotic substrates. On the basis of these data, we discuss how the BIRC6/SMAC complex can act as a stress-induced hub to regulate apoptosis and autophagy drivers.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Apoptose
/
Proteínas Mitocondriais
/
Proteínas Reguladoras de Apoptose
/
Proteínas Inibidoras de Apoptose
Limite:
Humans
Idioma:
En
Revista:
Science
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Áustria