9JJD

Structural analysis of autophagy-related protein 8a in Drosophila melanogaster

9JJD の概要

• エントリーDOI: 10.2210/pdb9jjd/pdb
• 分子名称: Autophagy-related 8a, isoform A (2 entities in total)
• 機能のキーワード: lipid tramsport, lipid binding protein, lipid transport
• 由来する生物種: Drosophila melanogaster (fruit fly)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 14416.56

構造登録者

Zhang, S.Q.,Luo, X.,Wu, D.X.,Liu, J.,Li, X.Y. (登録日: 2024-09-13, 公開日: 2025-03-26, 最終更新日: 2025-04-09)

主引用文献

Zhang, S.,Luo, X.,Yuan, X.,Wu, D.,Liu, J.,Zhao, K.,Xu, Y.,Zhou, J.,Li, X.,Li, Q.X.
Crystal Structure of Autophagy-Associated Protein 8 at 1.36 angstrom Resolution and Its Inhibitory Interactions with Indole Analogs.
J.Agric.Food Chem., 73:7111-7120, 2025

PubMed Abstract: Autophagy-associated protein 8 (ATG8) is essential for autophagy and organismal growth and development. In this study, we successfully resolved the crystal structure of () ATG8a (ATG8a) at 1.36 Å resolution. Being distinct from previously characterized ATG8 homologues, 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. 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 results demonstrated a strong affinity of 6-fluoroindole with ATG8a (3.54 μmol/L), but no affinity with the ATG8a mutant, suggesting that Lys48 is critical in binding 6-fluoroindole probably via a hydrogen bond interaction. The half-maximum lethal concentration (LC) of 6-fluoroindole against adult flies was 169 μg/mL. Our findings establish ATG8a as a promising target for developing indole-based insecticides.

PubMed: 40066832
DOI: 10.1021/acs.jafc.4c11205

実験手法

X-RAY DIFFRACTION (1.36 Å)