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 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.
Mesh Terms:
Amino Acid Motifs, Autophagy-Related Protein 8 Family, Autophagy-Related Proteins, Endopeptidases, Inositol Phosphates, Lipoylation, Microtubule-Associated Proteins, Multiprotein Complexes, Protein Binding, Protein Structure, Tertiary, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Ubiquitin-Conjugating Enzymes
EMBO J.
Date: Apr. 01, 2015
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