Structure of an ex vivoDrosophila TOM complex determined by single-particle cryoEM
Most mitochondrial precursor proteins are encoded in the cell nucleus and synthesized on cytoplasmic ribosomes. The translocase of the outer membrane (TOM) is the main protein-import pore of mitochondria, recognizing nascent precursors of mitochondrially targeted proteins and transferring them acros...
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International Union of Crystallography
2025-01-01
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| Online Access: | https://journals.iucr.org/paper?S2052252524011011 |
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| author | Agalya Periasamy Pamela Ornelas Thomas Bausewein Naomi Mitchell Jiamin Zhao Leonie M. Quinn Werner Kuehlbrandt Jacqueline M. Gulbis |
| author_facet | Agalya Periasamy Pamela Ornelas Thomas Bausewein Naomi Mitchell Jiamin Zhao Leonie M. Quinn Werner Kuehlbrandt Jacqueline M. Gulbis |
| author_sort | Agalya Periasamy |
| collection | DOAJ |
| description | Most mitochondrial precursor proteins are encoded in the cell nucleus and synthesized on cytoplasmic ribosomes. The translocase of the outer membrane (TOM) is the main protein-import pore of mitochondria, recognizing nascent precursors of mitochondrially targeted proteins and transferring them across the outer membrane. A 3.3 Å resolution map and molecular model of a TOM complex from Drosophila melanogaster, obtained by single-particle electron cryomicroscopy, is presented. As the first reported structure of a transgenic protein expressed and purified ex vivo from Drosophila, the method provides impetus for parallel structural and genetic analyses of protein complexes linked to human pathology. The core TOM complex extracted from native membranes of the D. melanogaster retina contains transgenic Tom40 co-assembled with four endogenous TOM components: Tom22, Tom5, Tom6 and Tom7. The Drosophila TOM structure presented here shows that the human and Drosophila TOM are very similar, with small conformational changes at two subunit interfaces attributable to variation in lipid-binding residues. The new structure provides an opportunity to pinpoint general features that differentiate the TOM structures of higher and unicellular eukaryotes. While the quaternary fold of the assembly is retained, local nuances of structural elements implicated in precursor import are indicative of subtle evolutionary change. |
| format | Article |
| id | doaj-art-c1a1deb4707c4c9e9d7d10c37b36854e |
| institution | Kabale University |
| issn | 2052-2525 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | International Union of Crystallography |
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| series | IUCrJ |
| spelling | doaj-art-c1a1deb4707c4c9e9d7d10c37b36854e2025-01-08T10:32:13ZengInternational Union of CrystallographyIUCrJ2052-25252025-01-01121496110.1107/S2052252524011011fq5025Structure of an ex vivoDrosophila TOM complex determined by single-particle cryoEMAgalya Periasamy0Pamela Ornelas1Thomas Bausewein2Naomi Mitchell3Jiamin Zhao4Leonie M. Quinn5Werner Kuehlbrandt6Jacqueline M. Gulbis7Structural Biology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, AustraliaDepartment of Structural Biology, Max Planck Institute of Biophysics, Max-von-Laue-Strasse 3, 60438 Frankfurt am Main, GermanyDepartment of Structural Biology, Max Planck Institute of Biophysics, Max-von-Laue-Strasse 3, 60438 Frankfurt am Main, GermanyDepartment of Cancer Biology and Therapeutics, John Curtin School of Medical Research, Australian National University (ANU), Canberra, ACT, AustraliaStructural Biology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, AustraliaDepartment of Cancer Biology and Therapeutics, John Curtin School of Medical Research, Australian National University (ANU), Canberra, ACT, AustraliaDepartment of Structural Biology, Max Planck Institute of Biophysics, Max-von-Laue-Strasse 3, 60438 Frankfurt am Main, GermanyStructural Biology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, AustraliaMost mitochondrial precursor proteins are encoded in the cell nucleus and synthesized on cytoplasmic ribosomes. The translocase of the outer membrane (TOM) is the main protein-import pore of mitochondria, recognizing nascent precursors of mitochondrially targeted proteins and transferring them across the outer membrane. A 3.3 Å resolution map and molecular model of a TOM complex from Drosophila melanogaster, obtained by single-particle electron cryomicroscopy, is presented. As the first reported structure of a transgenic protein expressed and purified ex vivo from Drosophila, the method provides impetus for parallel structural and genetic analyses of protein complexes linked to human pathology. The core TOM complex extracted from native membranes of the D. melanogaster retina contains transgenic Tom40 co-assembled with four endogenous TOM components: Tom22, Tom5, Tom6 and Tom7. The Drosophila TOM structure presented here shows that the human and Drosophila TOM are very similar, with small conformational changes at two subunit interfaces attributable to variation in lipid-binding residues. The new structure provides an opportunity to pinpoint general features that differentiate the TOM structures of higher and unicellular eukaryotes. While the quaternary fold of the assembly is retained, local nuances of structural elements implicated in precursor import are indicative of subtle evolutionary change.https://journals.iucr.org/paper?S2052252524011011mitochondrial translocasessingle-particle cryoemtom complexdrosophila melanogastermembrane proteinstom40macromolecular machines |
| spellingShingle | Agalya Periasamy Pamela Ornelas Thomas Bausewein Naomi Mitchell Jiamin Zhao Leonie M. Quinn Werner Kuehlbrandt Jacqueline M. Gulbis Structure of an ex vivoDrosophila TOM complex determined by single-particle cryoEM IUCrJ mitochondrial translocases single-particle cryoem tom complex drosophila melanogaster membrane proteins tom40 macromolecular machines |
| title | Structure of an ex vivoDrosophila TOM complex determined by single-particle cryoEM |
| title_full | Structure of an ex vivoDrosophila TOM complex determined by single-particle cryoEM |
| title_fullStr | Structure of an ex vivoDrosophila TOM complex determined by single-particle cryoEM |
| title_full_unstemmed | Structure of an ex vivoDrosophila TOM complex determined by single-particle cryoEM |
| title_short | Structure of an ex vivoDrosophila TOM complex determined by single-particle cryoEM |
| title_sort | structure of an ex vivodrosophila tom complex determined by single particle cryoem |
| topic | mitochondrial translocases single-particle cryoem tom complex drosophila melanogaster membrane proteins tom40 macromolecular machines |
| url | https://journals.iucr.org/paper?S2052252524011011 |
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