2. Academic Validation
  3. Cryo-EM structure of human mitochondrial trifunctional protein

Cryo-EM structure of human mitochondrial trifunctional protein

  • Proc Natl Acad Sci U S A. 2018 Jul 3;115(27):7039-7044. doi: 10.1073/pnas.1801252115.
Kai Liang 1 2 3,  Ningning Li 3 4 5,  Xiao Wang 3 6,  Jianye Dai 3 7,  Pulan Liu 1 3 4,  Chu Wang 3 7,  Xiao-Wei Chen 3 6,  Ning Gao 3 4 5,  Junyu Xiao 8 3 4
Affiliations

Affiliations

  • 1 State Key Laboratory of Protein and Plant Gene Research, Peking University, 100871 Beijing, China.
  • 2 Academy for Advanced Interdisciplinary Studies, Peking University, 100871 Beijing, China.
  • 3 Peking-Tsinghua Center for Life Sciences, Peking University, 100871 Beijing, China.
  • 4 School of Life Sciences, Peking University, 100871 Beijing, China.
  • 5 State Key Laboratory of Membrane Biology, Peking University, 100871 Beijing, China.
  • 6 Institute of Molecular Medicine, Peking University, 100871 Beijing, China.
  • 7 College of Chemistry and Molecular Engineering, Peking University, 100871 Beijing, China.
  • 8 State Key Laboratory of Protein and Plant Gene Research, Peking University, 100871 Beijing, China; junyuxiao@pku.edu.cn.
PMID: 29915090 DOI: 10.1073/pnas.1801252115
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 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.

Keywords

cryo-EM; fatty acid β-oxidation; mitochondrial trifunctional protein.

Figures