5ZRV

Structure of human mitochondrial trifunctional protein, octamer

Summary for 5ZRV

• Entry DOI: 10.2210/pdb5zrv/pdb
• EMDB information: 6940 6944 6945
• Descriptor: Trifunctional enzyme subunit alpha, mitochondrial, Trifunctional enzyme subunit beta, mitochondrial (2 entities in total)
• Functional Keywords: fatty acid beta-oxidation, cryo-em single-particle reconstruction, mitochondrial trifunctional protein, liase, oxidoreductase-transferase complex, oxidoreductase/transferase
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 8
• Total formula weight: 537891.94

Authors

Liang, K.,Li, N.,Dai, J.,Wang, X.,Liu, P.,Chen, X.,Wang, C.,Gao, N.,Xiao, J. (deposition date: 2018-04-25, release date: 2018-06-20, Last modification date: 2025-06-25)

Primary citation

Liang, K.,Li, N.,Wang, X.,Dai, J.,Liu, P.,Wang, C.,Chen, X.W.,Gao, N.,Xiao, J.
Cryo-EM structure of human mitochondrial trifunctional protein
Proc. Natl. Acad. Sci. U.S.A., 115:7039-7044, 2018

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 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.

PubMed: 29915090
DOI: 10.1073/pnas.1801252115

Experimental method

ELECTRON MICROSCOPY (7.7 Å)