title: PI3P binding by Atg21 organises Atg8 lipidation.
abstract: 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.
authors.affiliation: Georg-August-University, University Medicine, Institute of Cellular Biochemistry, Goettingen, Germany.
authors.forename: Lisa
authors.initials: L
authors.lastname: Juris
authors.affiliation: Georg-August-University, University Medicine, Institute of Cellular Biochemistry, Goettingen, Germany.
authors.forename: Marco
authors.initials: M
authors.lastname: Montino
authors.affiliation: Georg-August-University, University Medicine, Institute of Cellular Biochemistry, Goettingen, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Rube
authors.affiliation: Georg-August-University, University Medicine, Institute of Cellular Biochemistry, Goettingen, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Schlotterhose
authors.affiliation: Georg-August-University, University Medicine, Institute of Cellular Biochemistry, Goettingen, Germany mthumm@uni-goettingen.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Thumm
authors.affiliation: Georg-August-University, University Medicine, Institute of Cellular Biochemistry, Goettingen, Germany.
authors.forename: Roswitha
authors.initials: R
authors.lastname: Krick
mesh_terms: D020816:Amino Acid Motifs; D000071190:Autophagy-Related Protein 8 Family; D000071183:Autophagy-Related Proteins; D010450:Endopeptidases / Q000235:genetics / Q000378:metabolism*; D007295:Inositol Phosphates / Q000235:genetics / Q000378:metabolism*; D054878:Lipoylation / Q000502:physiology*; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D044763:Ubiquitin-Conjugating Enzymes / Q000235:genetics / Q000378:metabolism*
chemical_list: C113757:ATG8 protein, S cerevisiae; D000071190:Autophagy-Related Protein 8 Family; D000071183:Autophagy-Related Proteins; D007295:Inositol Phosphates; D008869:Microtubule-Associated Proteins; D046912:Multiprotein Complexes; D029701:Saccharomyces cerevisiae Proteins; D044763:Ubiquitin-Conjugating Enzymes; C450423:ATG21 protein, S cerevisiae; D010450:Endopeptidases; C104235:ATG3 protein, S cerevisiae
keywords: PROPPIN; WIPI; autophagy; ubiquitin‐like conjugation