Format

Send to

Choose Destination
EMBO J. 2015 Apr 1;34(7):955-73. doi: 10.15252/embj.201488957. Epub 2015 Feb 17.

PI3P binding by Atg21 organises Atg8 lipidation.

Author information

1
Georg-August-University, University Medicine, Institute of Cellular Biochemistry, Goettingen, Germany.
2
Georg-August-University, University Medicine, Institute of Cellular Biochemistry, Goettingen, Germany mthumm@uni-goettingen.de.

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.

KEYWORDS:

PROPPIN; WIPI; autophagy; ubiquitin‐like conjugation

PMID:
25691244
PMCID:
PMC4388602
DOI:
10.15252/embj.201488957
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Wiley Icon for PubMed Central
Loading ...
Support Center