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

• DOI: 10.1073/pnas.2301447120
• Publication Date: 2023-08-14T19:06:41Z
• Authors: Pamela Ornelas; Thomas Bausewein; Janosch Martin; Nina Morgner; Stephan Nussberger; Werner Kühlbrandt
• Keywords: 0301 basic medicine; 570; 03 medical and health sciences; Saccharomyces cerevisiae Proteins; Mitochondrial Precursor Protein Import Complex Proteins; Membrane Transport Proteins; Membrane Proteins; ddc:570; 612; Biological Sciences; Carrier Proteins; Mitochondrial Membrane Transport Proteins

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.