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Nature. 2019 Nov;575(7782):395-401. doi: 10.1038/s41586-019-1680-7. Epub 2019 Oct 10.

Structure of the mitochondrial import gate reveals distinct preprotein paths.

Author information

1
Faculty of Life Sciences, Kyoto Sangyo University, Kyoto, Japan.
2
Institute for Protein Dynamics, Kyoto Sangyo University, Kyoto, Japan.
3
Department of Clinical Laboratory Science, Division of Health Sciences, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan.
4
Department of Cell Biology and Anatomy, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
5
Institute of Biochemistry and Molecular Biology, ZBMZ, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
6
Spemann Graduate School of Biology and Medicine, University of Freiburg, Freiburg, Germany.
7
Institute of Molecular Precision Medicine and Hunan Key Laboratory of Molecular Precision Medicine, Xiangya Hospital, Central South University, Changsha, China.
8
Molecular Profiling Research Center for Drug Discovery (molprof), National Institute of Advanced Industrial Science and Technology (AIST), Tokyo, Japan.
9
Infection and Immunity Program, Biomedicine Discovery Institute and Department of Microbiology, Monash University, Melbourne, Victoria, Australia.
10
Organization for Promotion of Tenure Track, University of Miyazaki, Miyazaki, Japan.
11
Faculty of Biology, University of Freiburg, Freiburg, Germany.
12
Sanofi Deutschland, Frankfurt am Main, Germany.
13
Swiss Federal Institute of Technology (EPFL), Lausanne, Switzerland.
14
Nano Life Science Institute (WPI-Nano LSI), Kanazawa University, Kanazawa, Japan.
15
CIBSS Centre for Integrative Biological Signalling Studies, University of Freiburg, Freiburg, Germany.
16
Faculty of Life Sciences, Kyoto Sangyo University, Kyoto, Japan. tendo@cc.kyoto-su.ac.jp.
17
Institute for Protein Dynamics, Kyoto Sangyo University, Kyoto, Japan. tendo@cc.kyoto-su.ac.jp.

Abstract

The translocase of the outer mitochondrial membrane (TOM) is the main entry gate for proteins1-4. Here we use cryo-electron microscopy to report the structure of the yeast TOM core complex5-9 at 3.8-Å resolution. The structure reveals the high-resolution architecture of the translocator consisting of two Tom40 β-barrel channels and α-helical transmembrane subunits, providing insight into critical features that are conserved in all eukaryotes1-3. Each Tom40 β-barrel is surrounded by small TOM subunits, and tethered by two Tom22 subunits and one phospholipid. The N-terminal extension of Tom40 forms a helix inside the channel; mutational analysis reveals its dual role in early and late steps in the biogenesis of intermembrane-space proteins in cooperation with Tom5. Each Tom40 channel possesses two precursor exit sites. Tom22, Tom40 and Tom7 guide presequence-containing preproteins to the exit in the middle of the dimer, whereas Tom5 and the Tom40 N extension guide preproteins lacking a presequence to the exit at the periphery of the dimer.

PMID:
31600774
DOI:
10.1038/s41586-019-1680-7

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