Cited by 27Mitochondrial Function and PathologyAdvanced Electron Microscopy Techniques and ApplicationsProtein Structure and Dynamics

Two conformations of the Tom20 preprotein receptor in the TOM holo complex

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Ornelas, Pamela, Bausewein, Thomas, Martin, Janosch, Morgner, Nina, Nussberger, Stephan, Kühlbrandt, Werner·2023·Proceedings of the National Academy of Sciences

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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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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
Published
2023-08-14
Volume
120
Issue
34
Pages
e2301447120-e2301447120
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
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
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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