PI3P binding by Atg21 organises Atg8 lipidation. (17th February 2015)

• Record Type: Journal Article
• Authors: Juris, Lisa; Montino, Marco; Rube, Peter; Schlotterhose, Petra; Thumm, Michael; Krick, Roswitha
• Is Part Of: EMBO journal. Volume 34:Number 7(2015)
• Page Start: 955
• Page End: 973
• Publication Date: 2015-02-17
• Subjects: Molecular biology -- Periodicals; 572.805
• DOI: 10.15252/embj.201488957
• Languages: English
• ISSNs: 0261-4189

Abstract

<abstract abstract-type="main" id="embj201488957-abs-0001"> <title>Abstract</title> <p>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.</p> </abstract>