The amino-terminal region of Atg3 is essential for association with phosphatidylethanolamine in Atg8 lipidation

Autophagy is a bulk degradation process conserved among eukaryotes. In macro-autophagy, autophagosomes sequester cytoplasmic components and deliver their contents to lysosomes/vacuoles. Autophagosome formation requires the conjugation of Atg8, a ubiquitin-like protein, to phosphatidylethanolamine (PE). Here we report that the amino (N)-terminal region of Atg3, an E2-like enzyme for Atg8, plays a crucial role in Atg8–PE conjugation. The conjugating activities of Atg3 mutants lacking the 7 N-terminal amino acid residues or containing a Leu-to-Asp mutation at position 6 were severely impaired both in vivo and in vitro . In addition, the amino-terminal region is critical for interaction with the substrate, PE. MINT- 7010457: ATG8 (uniprotkb: P38182) and ATG3 (uniprotkb: P40344) bind (MI: 0407) by biochemical (MI: 0401)