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Tom40 protein import channel binds to non-native proteins and prevents their aggregation

Masatoshi Esaki1, Takashi Kanamori, Shuh-ichi Nishikawa

  • 1Department of Chemistry, Graduate School of Science, Nagoya University, Chikusa-ku, Nagoya 464-8602, Japan.

Nature Structural Biology
|November 5, 2003
PubMed

Insights

The translocator of the outer mitochondrial membrane (TOM) subunit Tom40 prevents aggregation of precursor proteins during mitochondrial import. This ensures efficient protein translocation by maintaining protein solubility within the Tom40 channel.

Area of Science:

  • Mitochondrial biology
  • Protein translocation
  • Molecular mechanisms

Background:

  • Mitochondria import proteins via the translocator of the outer mitochondrial membrane (TOM) complex.
  • Tom40 is a key subunit forming the protein-conducting channel within the TOM complex.

Purpose of the Study:

  • To elucidate the role of Tom40 in protein translocation across the mitochondrial outer membrane.
  • To investigate how Tom40 interacts with and affects precursor proteins during import.

Main Methods:

  • Site-specific photocrosslinking experiments to map protein interactions.
  • Biochemical assays using purified Tom40 and non-native proteins.
  • Inhibition studies to assess the impact of Tom40 binding on protein import.

Main Results:

  • Translocating precursor protein segments (up to 90 residues) were found associated with Tom40.
  • Purified Tom40 demonstrated binding to non-native proteins, inhibiting their aggregation.
  • A denatured protein bound to the Tom40 channel effectively blocked mitochondrial protein import.

Conclusions:

  • The Tom40 channel provides an optimized environment for translocating non-native precursor proteins.
  • Tom40 actively prevents precursor protein aggregation, facilitating their passage through the mitochondrial outer membrane.
  • This function contrasts with the ribosome's exit tunnel, highlighting a specialized role for Tom40 in protein import.

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