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-Structure paper
Title | Cryo-EM structure of human mitochondrial trifunctional protein. |
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Journal, issue, pages | Proc Natl Acad Sci U S A, Vol. 115, Issue 27, Page 7039-7044, Year 2018 |
Publish date | Jul 3, 2018 |
Authors | Kai Liang / Ningning Li / Xiao Wang / Jianye Dai / Pulan Liu / Chu Wang / Xiao-Wei Chen / Ning Gao / Junyu Xiao / |
PubMed Abstract | 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 ...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. |
External links | Proc Natl Acad Sci U S A / PubMed:29915090 / PubMed Central |
Methods | EM (single particle) |
Resolution | 4.2 - 7.7 Å |
Structure data | EMDB-6940, PDB-5zqz: EMDB-6944, PDB-5zrv: EMDB-6945: |
Source |
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Keywords | LYASE / HYDROLASE/TRANSFERASE / fatty acid beta-oxidation / cryo-EM single-particle reconstruction / mitochondrial trifunctional protein / HYDROLASE-TRANSFERASE complex / Liase / Oxidoreductase/Transferase / Oxidoreductase-Transferase complex |