Macroautophagy is a bulk degradation process induced by starvation in eukaryotic cells. In yeast, 15 Atg proteins coordinate the formation of autophagosomes. The pre-autophagosomal structure contains at least five Atg proteins: Atg1p, Atg2p, Atg5p, Aut7p/Atg8p and Atg16p, found in the vacuole [, ]. The C-terminal glycine of Atg12p is conjugated to a lysine residue of Atg5p via an isopeptide bond. During autophagy, cytoplasmic components are enclosed in autophagosomes and delivered to lysosomes/vacuoles. Autophagy protein 16 (Atg16) has been shown to bind to Atg5 and is required for the function of the Atg12p-Atg5p conjugate []. Autophagy protein 5 (Atg5) is directly required for the import of aminopeptidase I via the cytoplasm-to-vacuole targeting pathway [].This entry represents the C-terminal domain of Atg12, which is covalently bound to Atg5 [].
Atg10 is an E2-like enzyme required for the cytoplasm to vacuole transport (Cvt), autophagy and nucleophagy. It catalyses the conjugation of Atg12 to Atg5, which is required for proper localisation of Atg8 to the preautophagosomal structure (PAS) [].
This entry represents a group of ubiquitin-like-conjugating enzymes, including Atg3 and Atg10.Atg3 is the E2 enzyme for the LC3 lipidation process []. It is essential for autophagocytosis. The super protein complex, the Atg16L complex, consists of multiple Atg12-Atg5 conjugates. Atg16L has an E3-like role in the LC3 lipidation reaction. The activated intermediate, LC3-Atg3 (E2), is recruited to the site where the lipidation takes place []. Atg3 catalyses the conjugation of Atg8 and phosphatidylethanolamine (PE). Atg3 has an alpha/β-fold, and its core region is topologically similar to canonical E2 enzymes. Atg3 has two regions inserted in the core region and another with a long α-helical structure that protrudes from the core region as far as 30 A []. It interacts with atg8 through an intermediate thioester bond between Cys-288 and the C-terminal Gly of atg8. It also interacts with the C-terminal region of the E1-like atg7 enzyme.Atg10 acts as an E2-like enzyme that catalyzes the conjugation of ATG12 to ATG5 [].
