Multifaceted membrane interactions of human Atg3 promote LC3-phosphatidylethanolamine conjugation during autophagy
© 2023. Springer Nature Limited..
Autophagosome formation, a crucial step in macroautophagy (autophagy), requires the covalent conjugation of LC3 proteins to the amino headgroup of phosphatidylethanolamine (PE) lipids. Atg3, an E2-like enzyme, catalyzes the transfer of LC3 from LC3-Atg3 to PEs in targeted membranes. Here we show that the catalytically important C-terminal regions of human Atg3 (hAtg3) are conformationally dynamic and directly interact with the membrane, in collaboration with its N-terminal membrane curvature-sensitive helix. The functional relevance of these interactions was confirmed by in vitro conjugation and in vivo cellular assays. Therefore, highly curved phagophoric rims not only serve as a geometric cue for hAtg3 recruitment, but also their interaction with hAtg3 promotes LC3-PE conjugation by targeting its catalytic center to the membrane surface and bringing substrates into proximity. Our studies advance the notion that autophagosome biogenesis is directly guided by the spatial interactions of Atg3 with highly curved phagophoric rims.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:14 |
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| Enthalten in: |
Nature communications - 14(2023), 1 vom: 07. Sept., Seite 5503 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Ye, Yansheng [VerfasserIn] |
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| Links: |
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| Themen: |
Journal Article |
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| Anmerkungen: |
Date Completed 11.09.2023 Date Revised 12.02.2024 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1038/s41467-023-41243-4 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM361769482 |
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| 520 | |a © 2023. Springer Nature Limited. | ||
| 520 | |a Autophagosome formation, a crucial step in macroautophagy (autophagy), requires the covalent conjugation of LC3 proteins to the amino headgroup of phosphatidylethanolamine (PE) lipids. Atg3, an E2-like enzyme, catalyzes the transfer of LC3 from LC3-Atg3 to PEs in targeted membranes. Here we show that the catalytically important C-terminal regions of human Atg3 (hAtg3) are conformationally dynamic and directly interact with the membrane, in collaboration with its N-terminal membrane curvature-sensitive helix. The functional relevance of these interactions was confirmed by in vitro conjugation and in vivo cellular assays. Therefore, highly curved phagophoric rims not only serve as a geometric cue for hAtg3 recruitment, but also their interaction with hAtg3 promotes LC3-PE conjugation by targeting its catalytic center to the membrane surface and bringing substrates into proximity. Our studies advance the notion that autophagosome biogenesis is directly guided by the spatial interactions of Atg3 with highly curved phagophoric rims | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Phosphatidylethanolamines |2 NLM | |
| 700 | 1 | |a Tyndall, Erin R |e verfasserin |4 aut | |
| 700 | 1 | |a Bui, Van |e verfasserin |4 aut | |
| 700 | 1 | |a Bewley, Maria C |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Guifang |e verfasserin |4 aut | |
| 700 | 1 | |a Hong, Xupeng |e verfasserin |4 aut | |
| 700 | 1 | |a Shen, Yang |e verfasserin |4 aut | |
| 700 | 1 | |a Flanagan, John M |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Hong-Gang |e verfasserin |4 aut | |
| 700 | 1 | |a Tian, Fang |e verfasserin |4 aut | |
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