Structural overview of the translocase of the mitochondrial outer membrane complex
Most mitochondrial proteins are synthesized as precursor proteins (preproteins) in the cytosol and imported into mitochondria. The translocator of the outer membrane (TOM) complex functions as a main entry gate for the import of mitochondrial proteins. The TOM complex is a multi-subunit membrane pro...
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| Format: | Article |
| Language: | English |
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The Biophysical Society of Japan
2022-06-01
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| Series: | Biophysics and Physicobiology |
| Subjects: | |
| Online Access: | https://doi.org/10.2142/biophysico.bppb-v19.0022 |
| _version_ | 1811325627303723008 |
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| author | Yuhei Araiso Toshiya Endo |
| author_facet | Yuhei Araiso Toshiya Endo |
| author_sort | Yuhei Araiso |
| collection | DOAJ |
| description | Most mitochondrial proteins are synthesized as precursor proteins (preproteins) in the cytosol and imported into mitochondria. The translocator of the outer membrane (TOM) complex functions as a main entry gate for the import of mitochondrial proteins. The TOM complex is a multi-subunit membrane protein complex composed of a β-barrel channel Tom40 and six single-pass membrane proteins. Recent cryo-EM studies have revealed high-resolution structures of the yeast and human TOM complexes, which enabled us to discuss the mechanism of protein import at an amino-acid residue level. The cryo-EM structures show that two Tom40 β-barrels are surrounded by two sets of small Tom subunits to form a dimeric structure. The intermembrane space (IMS) domains of Tom40, Tom22, and Tom7 form a binding site for presequence-containing preproteins in the middle of the dimer to achieve their efficient transfer of to the downstream translocase, the TIM23 complex. The N-terminal segment of Tom40 spans the channel from the cytosol to the IMS to interact with Tom5 at the periphery of the dimer, where downstream components of presequence-lacking preproteins are recruited. Structure-based biochemical analyses together with crosslinking experiments revealed that each Tom40 channel possesses two distinct paths and exit sites for protein translocation of different sets of mitochondrial preproteins. Here we summarize the current knowledge on the structural features, protein translocation mechanisms, and remaining questions for the TOM complexes, with particular emphasis on their determined cryo-EM structures. This article is an extended version of the Japanese article, Structural basis for protein translocation by the translocase of the outer mitochondrial membrane, published in SEIBUTSU BUTSURI Vol. 60, p. 280-283 (2020). |
| first_indexed | 2024-04-13T14:36:31Z |
| format | Article |
| id | doaj.art-ebab3e6a5ff6402c9b0dbdf910211532 |
| institution | Directory Open Access Journal |
| issn | 2189-4779 |
| language | English |
| last_indexed | 2024-04-13T14:36:31Z |
| publishDate | 2022-06-01 |
| publisher | The Biophysical Society of Japan |
| record_format | Article |
| series | Biophysics and Physicobiology |
| spelling | doaj.art-ebab3e6a5ff6402c9b0dbdf9102115322022-12-22T02:43:02ZengThe Biophysical Society of JapanBiophysics and Physicobiology2189-47792022-06-011910.2142/biophysico.bppb-v19.0022Structural overview of the translocase of the mitochondrial outer membrane complexYuhei Araiso0Toshiya Endo1Department of Clinical Laboratory Science, Division of Health Sciences, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa 920-0942, JapanFaculty of Life Sciences, Kyoto Sangyo University, Kyoto 603-8555, JapanMost mitochondrial proteins are synthesized as precursor proteins (preproteins) in the cytosol and imported into mitochondria. The translocator of the outer membrane (TOM) complex functions as a main entry gate for the import of mitochondrial proteins. The TOM complex is a multi-subunit membrane protein complex composed of a β-barrel channel Tom40 and six single-pass membrane proteins. Recent cryo-EM studies have revealed high-resolution structures of the yeast and human TOM complexes, which enabled us to discuss the mechanism of protein import at an amino-acid residue level. The cryo-EM structures show that two Tom40 β-barrels are surrounded by two sets of small Tom subunits to form a dimeric structure. The intermembrane space (IMS) domains of Tom40, Tom22, and Tom7 form a binding site for presequence-containing preproteins in the middle of the dimer to achieve their efficient transfer of to the downstream translocase, the TIM23 complex. The N-terminal segment of Tom40 spans the channel from the cytosol to the IMS to interact with Tom5 at the periphery of the dimer, where downstream components of presequence-lacking preproteins are recruited. Structure-based biochemical analyses together with crosslinking experiments revealed that each Tom40 channel possesses two distinct paths and exit sites for protein translocation of different sets of mitochondrial preproteins. Here we summarize the current knowledge on the structural features, protein translocation mechanisms, and remaining questions for the TOM complexes, with particular emphasis on their determined cryo-EM structures. This article is an extended version of the Japanese article, Structural basis for protein translocation by the translocase of the outer mitochondrial membrane, published in SEIBUTSU BUTSURI Vol. 60, p. 280-283 (2020).https://doi.org/10.2142/biophysico.bppb-v19.0022mitochondriaprotein translocationtom complex preproteincryo-em |
| spellingShingle | Yuhei Araiso Toshiya Endo Structural overview of the translocase of the mitochondrial outer membrane complex Biophysics and Physicobiology mitochondria protein translocation tom complex preprotein cryo-em |
| title | Structural overview of the translocase of the mitochondrial outer membrane complex |
| title_full | Structural overview of the translocase of the mitochondrial outer membrane complex |
| title_fullStr | Structural overview of the translocase of the mitochondrial outer membrane complex |
| title_full_unstemmed | Structural overview of the translocase of the mitochondrial outer membrane complex |
| title_short | Structural overview of the translocase of the mitochondrial outer membrane complex |
| title_sort | structural overview of the translocase of the mitochondrial outer membrane complex |
| topic | mitochondria protein translocation tom complex preprotein cryo-em |
| url | https://doi.org/10.2142/biophysico.bppb-v19.0022 |
| work_keys_str_mv | AT yuheiaraiso structuraloverviewofthetranslocaseofthemitochondrialoutermembranecomplex AT toshiyaendo structuraloverviewofthetranslocaseofthemitochondrialoutermembranecomplex |