Cryo-EM structure of human mitochondrial trifunctional protein.
Proc Natl Acad Sci U S A
; 115(27): 7039-7044, 2018 07 03.
Article
en En
| MEDLINE
| ID: mdl-29915090
ABSTRACT
The mitochondrial trifunctional protein (TFP) catalyzes three reactions in the fatty acid ß-oxidation process. Mutations in the two TFP subunits cause mitochondrial trifunctional protein deficiency and acute fatty liver of pregnancy that can lead to death. Here we report a 4.2-Å cryo-electron microscopy α2ß2 tetrameric structure of the human TFP. The tetramer has a V-shaped architecture that displays a distinct assembly compared with the bacterial TFPs. A concave surface of the TFP tetramer interacts with the detergent molecules in the structure, suggesting that this region is involved in associating with the membrane. Deletion of a helical hairpin in TFPß decreases its binding to the liposomes in vitro and reduces its membrane targeting in cells. Our results provide the structural basis for TFP function and have important implications for fatty acid oxidation related diseases.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Microscopía por Crioelectrón
/
Proteína Trifuncional Mitocondrial
Límite:
Humans
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Año:
2018
Tipo del documento:
Article
País de afiliación:
China