Cryo-EM structure of human mitochondrial trifunctional protein

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 micros...

Full description

Saved in:
Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2018-07, Vol.115 (27), p.7039-7044
Main Authors: Liang, Kai, Li, Ningning, Wang, Xiao, Dai, Jianye, Liu, Pulan, Wang, Chu, Chen, Xiao-Wei, Gao, Ning, Xiao, Junyu
Format: Article
Language:English
Subjects:
Biological Sciences
Chemical reactions
Clonal deletion
Cryoelectron Microscopy
Electron microscopy
Fatty acids
Fatty liver
Humans
Liposomes
Liver
Metabolism
Mitochondria
Mitochondrial Trifunctional Protein - metabolism
Mitochondrial Trifunctional Protein - ultrastructure
Molecular structure
Mutation
Oxidation
Oxidation process
Pregnancy
Pregnancy complications
Protein deficiency
Protein Structure, Quaternary
Protein Structure, Secondary
Proteins
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1801252115