Two conformations of the Tom20 preprotein receptor in the TOM holo complex
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Abstract
The TOM complex is the main entry point for precursor proteins (preproteins) into mitochondria. Preproteins containing targeting sequences are recognized by the TOM complex and imported into mitochondria. We have determined the structure of the TOM core complex from Neurospora crassa by single-particle electron cryomicroscopy at 3.3 Å resolution, showing its interaction with a bound preprotein at 4 Å resolution, and of the TOM holo complex including the Tom20 receptor at 6 to 7 Å resolution. TOM is a transmembrane complex consisting of two β-barrels, three receptor subunits, and three short transmembrane subunits. Tom20 has a transmembrane helix and a receptor domain on the cytoplasmic side. We propose that Tom20 acts as a dynamic gatekeeper, guiding preproteins into the pores of the TOM complex. We analyze the interactions of Tom20 with other TOM subunits, present insights into the structure of the TOM holo complex, and suggest a translocation mechanism.
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Cites
Highly accurate protein structure prediction with AlphaFold
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Structure of human PINK1 at a mitochondrial TOM-VDAC array
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- Authors
- Ornelas, P., Bausewein, T., Martin, J., Morgner, N., Nussberger, S., & Kühlbrandt, W.
- Affiliations
- Max Planck Institute of Biophysics (DE)
- Goethe University Frankfurt (DE)
- University of Stuttgart (DE)
- Corresponding author
- Kühlbrandt, Werner
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2023-08-14
- Volume
- 120
- Issue
- 34
- Pages
- e2301447120-e2301447120
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC10450662
- OpenAlex
- W4385802127
- Cited by
- 27
- References
- 3
- Citations by year
- 2026: 5 · 2025: 12 · 2024: 9 · 2023: 1
- FWCI
- 2.40
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Publication Server of Goethe University Frankfurt am Main (Goethe University Frankfurt) (submittedVersion, cc-by-nc)
- Funders
- Consejo Nacional de Ciencia y Tecnología
- Max-Planck-Gesellschaft
- Universität Stuttgart
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Structural Biology › Advanced Electron Microscopy Techniques and Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Keywords
- TOM complex, Tom20, mitochondrial protein import, Neurospora crassa, translocation mechanism, protein conformation
- MeSH terms
- Mitochondrial Precursor Protein Import Complex Proteins, Carrier Proteins, Membrane Proteins, Membrane Transport Proteins, Saccharomyces cerevisiae Proteins, Mitochondrial Membrane Transport Proteins
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