Portal de investigación
COQ8 chaperones coenzyme Q lipid intermediates through ATP-driven structural gating.
Fecha de publicación:
Fecha Ahead of Print:
Autores de IIS La Fe
Participantes ajenos a IIS La Fe
- Gottinger A
- Malatesta M
- Nicoll CR
- Ansari G
- Quinodoz M
- Kaminska K
- Tang RWC
- Tan TE
- Fenner BJ
- Pfau M
- Burbach NE
- Cecchini D
- Rivolta C
- Mattevi A
Grupos
Abstract
Coenzyme Q biosynthesis requires two atypical kinase-like proteins (COQ8A and COQ8B), whose detailed molecular mechanism remains unclear. Here, we show that both paralogs function as adenosine triphosphatases (ATPases) that promote coenzyme Q biosynthetic metabolon activity by engaging in loose protein-protein interactions and delivering insoluble biosynthetic intermediates. Structural bioinformatics and pathological variant-driven mutagenesis identify a previously uncharacterized pocket that selectively recognizes coenzyme Q biosynthetic intermediates via their head groups. X-ray crystallography reveals that access to this pocket is gated by long-range conformational changes controlled by adenosine 5'-triphosphate hydrolysis. Last, excess coenzyme Q suppresses binding of early-stage intermediates and thereby abolishes the promoting effect of COQ8 on the metabolon. Together, these findings support a model in which COQ8 tunes coenzyme Q biosynthesis by coupling ATPase-driven intermediate chaperoning to feedback inhibition by the final product.
Datos de la publicación
- ISSN/ISSNe:
- 2375-2548, 2375-2548
- Tipo:
- Article
- Páginas:
- -
- PubMed:
- 42525751
- Factor de Impacto:
- 4,586 SCImago ℠
- Cuartil:
- Q1 SCImago ℠
Science Advances AMER ASSOC ADVANCEMENT SCIENCE
Documentos
Filiaciones
Cita
Gottinger A,Malatesta M,Nicoll CR,Ansari G,Quinodoz M,Kaminska K,Tang RWC,Tan T-E,Fenner BJ,BARBERÁN P,GARCÍA G,MILLÁN JM,Pfau M,Burbach NE,Cecchini D,Rivolta C,Mattevi A. COQ8 chaperones coenzyme Q lipid intermediates through ATP-driven structural gating. Sci. Adv. 2026. 12. (31):eaeg1124. IF:13,900. (1).