期刊
NATURE
卷 575, 期 7782, 页码 395-+出版社
NATURE RESEARCH
DOI: 10.1038/s41586-019-1680-7
关键词
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资金
- JSPS KAKENHI [15H05705, 2222703, 16K21680, 18K11543, 19K16077, 18KK0197, 26119003]
- JST CREST [JPMJCR12M1, JPMJCR14M1]
- European Research Council (ERC) [648235]
- Deutsche Forschungsgemeinschaft [BE 4679/2-2, PF 202/9-1]
- Germany's Excellence Strategy [390939984]
- Takeda Science Foundation
- Platform Project for Supporting Drug Discovery and Life Science Research (Basis for Supporting Innovative Drug Discovery and Life Science Research (BINDS)) from AMED [JP19am01011115, JP19am0101114]
- Ichiro Kanehara Foundation for the Promotion of Medical Sciences and Medical Care, Waksman Foundation of Japan, Tokyo Biochemical Research Foundation
- Sumitomo Foundation
- Naito Foundation
- Uehara Memorial Foundation
- Australian Research Council [DP160100227]
- Research Fellowship for Young Scientists from the Japan Society of the Promotion of Science [15J07687]
- Grants-in-Aid for Scientific Research [19K16077, 15J07687, 16K21680, 18K11543, 18KK0197, 26119003] Funding Source: KAKEN
The translocase of the outer mitochondrial membrane (TOM) is the main entry gate for proteins(1-4). Here we use cryo-electron microscopy to report the structure of the yeast TOM core complex(5-9) at 3.8-angstrom resolution. The structure reveals the high-resolution architecture of the translocator consisting of two Tom40 beta-barrel channels and a-helical transmembrane subunits, providing insight into critical features that are conserved in all eukaryotes(1-3). Each Tom40 beta-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.
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