ABSTRACT

Atg8 has attracted attention as a central factor in autophagosome biogenesis for a long time. However, the molecular activities of Atg8 on the phagophore membranes as the physiologically functional lipidated form remain enigmatic. In our recent study, we unveiled the hidden physicochemical activity of lipidated Atg8 toward the membrane. Structural analysis revealed that lipidated Atg8 adopts a preferred orientation on the membrane, contacting the membrane using aromatic residues and at the same time exposing cargo binding pockets to the solvent, enabling this small protein to perturb and transform membranes while recognizing autophagic cargos. The membrane perturbation activity was shown to be essential for efficient autophagosome biogenesis, yet questions on the mechanistic roles of Atg8 remain open.

摘要

长期以来，Atg8 作为自噬体生物发生的中心因素引起了人们的关注。然而，作为具有生理功能的脂化形式，Atg8 在吞噬细胞膜上的分子活性仍然是个谜。在我们最近的研究中，我们揭示了脂化 Atg8 对膜的隐藏物理化学活性。结构分析表明，脂化的 Atg8 在膜上采用优先取向，使用芳香残基与膜接触，同时将货物结合袋暴露于溶剂，使这种小蛋白能够在识别自噬货物的同时扰乱和转化膜。膜扰动活性被证明对于有效的自噬体生物发生至关重要，但关于 Atg8 的机制作用的问题仍然存在。