Macroautophagy (hereafter referred to as autophagy) is a highly conserved catabolic eukaryotic pathway that is critical for stress responses and homeostasis. Atg18, one of the core proteins involved in autophagy, belongs to the PROPPIN family and is composed of seven WD40 repeats. Together with Atg2, Atg18 participates in the elongation of phagophores and the recycling of Atg9 in yeast. Despite extensive studies on the PROPPIN family, the structure of Atg18 from Saccharomyces cerevisiae has not been determined. Here, we report the structure of ScAtg18 at a resolution of 2.8 Å. Based on bioinformatics and structural analysis, we found that the 7AB loop of ScAtg18 is extended in Atg18, in comparison to other members of the PROPPIN family. Genetic analysis revealed that the 7AB loop of ScAtg18 is required for autophagy. Biochemical and biophysical experiments indicated that the 7AB loop of ScAtg18 is critical for interaction with ScAtg2 and the recruitment of ScAtg2 to the autophagy-initiating site. Collectively, our results show that the 7AB loop of ScAtg18 is a new binding site for Atg2 and is of functional importance to autophagy.

巨自噬（以下称为自噬）是高度保守的分解代谢真核途径，对应激反应和体内稳态至关重要。Atg18是自噬的核心蛋白之一，属于PROPPIN家族，由七个WD40重复序列组成。Atg18与Atg2一起参与了噬菌体的延长和酵母中Atg9的回收。尽管对PROPPIN家族进行了广泛的研究，但酿酒酵母Atg18的结构 尚未确定。在这里，我们以2.8Å的分辨率报告ScAtg18的结构。基于生物信息学和结构分析，我们发现，与PROPPIN家族的其他成员相比，ScAtg18的7AB环在Atg18中得到了扩展。遗传分析表明，ScAtg18的7AB环是自噬所必需的。生化和生物物理实验表明，ScAtg18的7AB环对于与ScAtg2相互作用以及将ScAtg2募集到自噬起始位点至关重要。总的来说，我们的结果表明，ScAtg18的7AB环是Atg2的新结合位点，对自噬具有重要的功能。