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-Structure paper
Title | Molecular pathway of mitochondrial preprotein import through the TOM-TIM23 supercomplex. |
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Journal, issue, pages | Nat Struct Mol Biol, Vol. 30, Issue 12, Page 1996-2008, Year 2023 |
Publish date | Sep 11, 2023 |
Authors | Xueyin Zhou / Yuqi Yang / Guopeng Wang / Shanshan Wang / Dongjie Sun / Xiaomin Ou / Yuke Lian / Long Li / |
PubMed Abstract | Over half of mitochondrial proteins are imported from the cytosol via the pre-sequence pathway, controlled by the TOM complex in the outer membrane and the TIM23 complex in the inner membrane. The ...Over half of mitochondrial proteins are imported from the cytosol via the pre-sequence pathway, controlled by the TOM complex in the outer membrane and the TIM23 complex in the inner membrane. The mechanisms through which proteins are translocated via the TOM and TIM23 complexes remain unclear. Here we report the assembly of the active TOM-TIM23 supercomplex of Saccharomyces cerevisiae with translocating polypeptide substrates. Electron cryo-microscopy analyses reveal that the polypeptide substrates pass the TOM complex through the center of a Tom40 subunit, interacting with a glutamine-rich region. Structural and biochemical analyses show that the TIM23 complex contains a heterotrimer of the subunits Tim23, Tim17 and Mgr2. The polypeptide substrates are shielded from lipids by Mgr2 and Tim17, which creates a translocation pathway characterized by a negatively charged entrance and a central hydrophobic region. These findings reveal an unexpected pre-sequence pathway through the TOM-TIM23 supercomplex spanning the double membranes of mitochondria. |
External links | Nat Struct Mol Biol / PubMed:37696957 |
Methods | EM (single particle) |
Resolution | 4.1 - 9.36 Å |
Structure data | EMDB-34660, PDB-8hco: EMDB-34661: TOM-TIM23 supercomplex with a GFP containing substrate |
Source |
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Keywords | PROTEIN TRANSPORT / Mitochondrial protein import / TOM / protein translocation |