biostudies-literatureZhang SU.S. Department of AgricultureScience and Technology Program of Guizhou ProvinceNational Natural Science Foundation of ChinaTalents of Guizhou Science and Technology Cooperation PlatformNational Key Research and Development Program of China7111-7120https://www.ebi.ac.uk/biostudies/studies/S-EPMC11951139biostudies-literatureUnknown73(12)Autophagy-associated protein 8 (ATG8) is essential for autophagy and organismal growth and development. In this study, we successfully resolved the crystal structure of <i>Drosophila melanogaster</i> (<i>D. melanogaster</i>) ATG8a (<i>Dm</i>ATG8a) at 1.36 Å resolution. Being distinct from previously characterized ATG8 homologues, <i>Dm</i>ATG8a (121 residues) adopts a unique fold comprising five α-helices and four β-folding strands, in contrast to the canonical four α-helices and four β-folding strands observed in other ATG8 proteins. <i>Dm</i>ATG8a features two active cavities: hydrophobic pocket 1 (HP1) and hydrophobic pocket 2 (HP2), which are essential for the normal physiological function of ATG8. Indole and its analogs can bind specifically with HP1. Microscale thermophoresis resultsJournal of agricultural and food chemistryCrystal Structure of Autophagy-Associated Protein 8 at 1.36 A Resolution and Its Inhibitory Interactions with Indole Analogs.PMC11951139323300872021YFD1700100HAW05044R(2021)562332172461HAW05020H(2024)007Li XLiu JLi QXLuo XWu DZhang SYuan XZhao KXu YZhou JfalseCrystal Structure of Autophagy-Associated Protein 8 at 1.36 A Resolution and Its Inhibitory Interactions with Indole Analogs.Autophagy-associated protein 8 (ATG8) is essential for autophagy and organismal growth and development. In this study, we successfully resolved the crystal structure of <i>Drosophila melanogaster</i> (<i>D. melanogaster</i>) ATG8a (<i>Dm</i>ATG8a) at 1.36 Å resolution. Being distinct from previously characterized ATG8 homologues, <i>Dm</i>ATG8a (121 residues) adopts a unique fold comprising five α-helices and four β-folding strands, in contrast to the canonical four α-helices and four β-folding strands observed in other ATG8 proteins. <i>Dm</i>ATG8a features two active cavities: hydrophobic pocket 1 (HP1) and hydrophobic pocket 2 (HP2), which are essential for the normal physiological function of ATG8. Indole and its analogs can bind specifically with HP1. Microscale thermophoresis results2025-01-01T00:00:00Z2025 Mar2026-06-02T07:23:15.562Z2026-04-15T03:15:14.752ZS-EPMC119511394006683210.1021/acs.jafc.4c11205