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Structure of the mitochondrial import gate reveals distinct preprotein paths.

Araiso Y, Tsutsumi A, Qiu J, Imai K, Shiota T, Song J, Lindau C, Wenz LS, Sakaue H, Yunoki K, Kawano S, Suzuki J, Wischnewski M, Schütze C, Ariyama H, Ando T, Becker T, Lithgow T, Wiedemann N, Pfanner N, Kikkawa M, Endo T
Nature 575 395-401 (2019)
Cited: 82 times
EuropePMC logo PMID: 31600774

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.

Reviews - 6jnf mentioned but not cited (3)

  1. A Biochemical and Structural Understanding of TOM Complex Interactions and Implications for Human Health and Disease. Pitt AS, Buchanan SK. Cells 10 1164 (2021)
  2. Building Better Barrels - β-barrel Biogenesis and Insertion in Bacteria and Mitochondria. Diederichs KA, Buchanan SK, Botos I. J Mol Biol 433 166894 (2021)
  3. Targeting and Insertion of Membrane Proteins in Mitochondria. Eaglesfield R, Tokatlidis K. Front Cell Dev Biol 9 803205 (2021)

Articles - 6jnf mentioned but not cited (5)

  1. Spatial arrangement of proteins in planar and curved membranes by PPM 3.0. Lomize AL, Todd SC, Pogozheva ID. Protein Sci 31 209-220 (2022)
  2. Mapping protein interactions in the active TOM-TIM23 supercomplex. Gomkale R, Linden A, Neumann P, Schendzielorz AB, Stoldt S, Dybkov O, Kilisch M, Schulz C, Cruz-Zaragoza LD, Schwappach B, Ficner R, Jakobs S, Urlaub H, Rehling P. Nat Commun 12 5715 (2021)
  3. Letter Structural insights into assembly of human mitochondrial translocase TOM complex. Guan Z, Yan L, Wang Q, Qi L, Hong S, Gong Z, Yan C, Yin P. Cell Discov 7 22 (2021)
  4. The receptor subunit Tom20 is dynamically associated with the TOM complex in mitochondria of human cells. Bhagawati M, Arroum T, Webeling N, Montoro AG, Mootz HD, Busch KB. Mol Biol Cell 32 br1 (2021)
  5. Structural overview of the translocase of the mitochondrial outer membrane complex. Araiso Y, Endo T. Biophys Physicobiol 19 e190022 (2022)


Reviews citing this publication (35)

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Articles citing this publication (39)

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  36. Letter The architecture of substrate-engaged TOM-TIM23 supercomplex reveals preprotein proximity sites for mitochondrial protein translocation. Wang Q, Zhuang J, Huang R, Guan Z, Yan L, Hong S, Zhang L, Huang C, Liu Z, Yin P. Cell Discov 10 19 (2024)
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