Cryo-EM structure of human mitochondrial trifunctional protein.
Kai LiangNingning LiXiao WangJianye DaiPulan LiuChu WangXiao-Wei ChenNing GaoJunyu XiaoPublished in: Proceedings of the National Academy of Sciences of the United States of America (2018)
The mitochondrial trifunctional protein (TFP) catalyzes three reactions in the fatty acid β-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 α2β2 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 TFPβ 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.
Keyphrases
- fatty acid
- electron microscopy
- endothelial cells
- oxidative stress
- structural basis
- binding protein
- protein protein
- induced apoptosis
- amino acid
- induced pluripotent stem cells
- liver failure
- high resolution
- pluripotent stem cells
- cell death
- nitric oxide
- cancer therapy
- preterm birth
- signaling pathway
- endoplasmic reticulum stress
- respiratory failure
- pregnancy outcomes
- aortic dissection
- acute respiratory distress syndrome