Structural basis of Tom20 and Tom22 cytosolic domains as the human TOM complex receptors
Mitochondrial preproteins synthesized in cytosol are imported into mitochondria by a multisubunit translocase of the outer membrane (TOM) complex. Functioned as the receptor, the TOM complex components, Tom 20, Tom22, and Tom70, recognize the presequence and further guide the protein translocation. Their deficiency has been linked with neurodegenerative diseases and cardiac pathology. Although several structures of the TOM complex have been reported by cryoelectron microscopy (cryo-EM), how Tom22 and Tom20 function as TOM receptors remains elusive. Here we determined the structure of TOM core complex at 2.53 Å and captured the structure of the TOM complex containing Tom22 and Tom20 cytosolic domains at 3.74 Å. Structural analysis indicates that Tom20 and Tom22 share a similar three-helix bundle structural feature in the cytosolic domain. Further structure-guided biochemical analysis reveals that the Tom22 cytosolic domain is responsible for binding to the presequence, and the helix H1 is critical for this binding. Altogether, our results provide insights into the functional mechanism of the TOM complex recognizing and transferring preproteins across the mitochondrial membrane.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:119 |
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| Enthalten in: |
Proceedings of the National Academy of Sciences of the United States of America - 119(2022), 26 vom: 28. Juni, Seite e2200158119 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Su, Jiayue [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 24.06.2022 Date Revised 23.12.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1073/pnas.2200158119 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM342544047 |
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| 100 | 1 | |a Su, Jiayue |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Structural basis of Tom20 and Tom22 cytosolic domains as the human TOM complex receptors |
| 264 | 1 | |c 2022 | |
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| 500 | |a Date Completed 24.06.2022 | ||
| 500 | |a Date Revised 23.12.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Mitochondrial preproteins synthesized in cytosol are imported into mitochondria by a multisubunit translocase of the outer membrane (TOM) complex. Functioned as the receptor, the TOM complex components, Tom 20, Tom22, and Tom70, recognize the presequence and further guide the protein translocation. Their deficiency has been linked with neurodegenerative diseases and cardiac pathology. Although several structures of the TOM complex have been reported by cryoelectron microscopy (cryo-EM), how Tom22 and Tom20 function as TOM receptors remains elusive. Here we determined the structure of TOM core complex at 2.53 Å and captured the structure of the TOM complex containing Tom22 and Tom20 cytosolic domains at 3.74 Å. Structural analysis indicates that Tom20 and Tom22 share a similar three-helix bundle structural feature in the cytosolic domain. Further structure-guided biochemical analysis reveals that the Tom22 cytosolic domain is responsible for binding to the presequence, and the helix H1 is critical for this binding. Altogether, our results provide insights into the functional mechanism of the TOM complex recognizing and transferring preproteins across the mitochondrial membrane | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a TOM complex | |
| 650 | 4 | |a Tom20 | |
| 650 | 4 | |a Tom22 | |
| 650 | 4 | |a cryo-EM | |
| 650 | 4 | |a mitochondria | |
| 650 | 7 | |a Mitochondrial Precursor Protein Import Complex Proteins |2 NLM | |
| 650 | 7 | |a Receptors, Cytoplasmic and Nuclear |2 NLM | |
| 650 | 7 | |a TOMM20 protein, human |2 NLM | |
| 650 | 7 | |a TOMM22 protein, human |2 NLM | |
| 700 | 1 | |a Liu, Desheng |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Fan |e verfasserin |4 aut | |
| 700 | 1 | |a Zuo, Mei-Qing |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Chang |e verfasserin |4 aut | |
| 700 | 1 | |a Dong, Meng-Qiu |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, Shan |e verfasserin |4 aut | |
| 700 | 1 | |a Sui, Sen-Fang |e verfasserin |4 aut | |
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| 773 | 1 | 8 | |g volume:119 |g year:2022 |g number:26 |g day:28 |g month:06 |g pages:e2200158119 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1073/pnas.2200158119 |3 Volltext |
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