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PI3P binding by Atg21 organises Atg8 lipidation

Autophagosome biogenesis requires two ubiquitin‐like conjugation systems. One couples ubiquitin‐like Atg8 to phosphatidylethanolamine, and the other couples ubiquitin‐like Atg12 to Atg5. Atg12~Atg5 then forms a heterodimer with Atg16. Membrane recruitment of the Atg12~Atg5/Atg16 complex defines the...

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Bibliographic Details
Published in:The EMBO journal 2015-04, Vol.34 (7), p.955-973
Main Authors: Juris, Lisa, Montino, Marco, Rube, Peter, Schlotterhose, Petra, Thumm, Michael, Krick, Roswitha
Format: Article
Language:English
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Summary:Autophagosome biogenesis requires two ubiquitin‐like conjugation systems. One couples ubiquitin‐like Atg8 to phosphatidylethanolamine, and the other couples ubiquitin‐like Atg12 to Atg5. Atg12~Atg5 then forms a heterodimer with Atg16. Membrane recruitment of the Atg12~Atg5/Atg16 complex defines the Atg8 lipidation site. Lipidation requires a PI3P‐containing precursor. How PI3P is sensed and used to coordinate the conjugation systems remained unclear. Here, we show that Atg21, a WD40 β‐propeller, binds via PI3P to the preautophagosomal structure (PAS). Atg21 directly interacts with the coiled‐coil domain of Atg16 and with Atg8. This latter interaction requires the conserved F5K6‐motif in the N‐terminal helical domain of Atg8, but not its AIM‐binding site. Accordingly, the Atg8 AIM‐binding site remains free to mediate interaction with its E2 enzyme Atg3. Atg21 thus defines PI3P‐dependently the lipidation site by linking and organising the E3 ligase complex and Atg8 at the PAS. Synopsis Atg21 binds to PI3P at the preautophagosomal structure, recruits ubiquitin‐like Atg8 and the E3 ligase complex Atg12~Atg5/Atg16 and arranges them for efficient lipidation of Atg8. Atg21 binds via PI3P to the preautophagosomal structure (PAS). Atg21 interacts with the coiled‐coil domain of Atg16 and thus recruits the E3 ligase complex Atg12˜Atg5/Atg16 to the PAS. Atg21 interacts with ubiquitin‐like Atg8. Atg21 arranges the E3 ligase complex and Atg8 at the PAS for efficient lipidation of Atg8. Graphical Abstract Atg21 binds to PI3P at the preautophagosomal structure, recruits ubiquitin‐like Atg8 and the E3 ligase complex Atg12~Atg5/Atg16 and arranges them for efficient lipidation of Atg8.
ISSN:0261-4189
1460-2075
DOI:10.15252/embj.201488957