The crystal structure of Atg18 reveals a new binding site for Atg2 inSaccharomyces cerevisiae
The crystal structure of Atg18 reveals a new binding site for Atg2 inSaccharomyces cerevisiae
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Atg18的晶体结构揭示了酿酒酵母中Atg2的新结合位点
DOI：
10.1007/s00018-020-03621-9
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发表时间：
2020-08-18
影响因子：
8
通讯作者：
Lu, Kefeng
中科院分区：
文献类型：
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作者：
Lei, Yuqing;Tang, Dan;Lu, Kefeng
大自噬（Macroautophagy，以下简称自噬）是一种高度保守的分解代谢真核生物途径，对应激反应和体内平衡至关重要。Atg18是参与自噬的核心蛋白之一，属于PROPPIN家族，由7个WD 40重复序列组成。与Atg 2一起，Atg 18参与吞噬细胞的延伸和Atg 9在酵母中的再循环。尽管对PROPPIN家族进行了广泛的研究，但酿酒酵母Atg 18的结构尚未确定。在这里，我们报告的结构ScAtg18在2.8埃的分辨率。基于生物信息学和结构分析，我们发现ScAtg18的7AB环在Atg18中延伸，与PROPPIN家族的其他成员相比。遗传分析显示ScAtg18的7AB环是自噬所必需的。生化和生物物理实验表明，ScAtg 18的7AB环对于与ScAtg 2的相互作用以及ScAtg 2招募到自噬起始位点至关重要。总的来说，我们的研究结果表明，ScAtg18的7AB环是一个新的结合位点的Atg2和自噬功能的重要性。
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 fromSaccharomyces cerevisiae has not been determined. Here, we report the structure of ScAtg18 at a resolution of 2.8 angstrom. 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.