The crystal structure of Atg18 reveals a new binding site for Atg2 in Saccharomyces cerevisiae.

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.

Citation

Yuqing Lei, Dan Tang, Ga Liao, Liangting Xu, Shiyan Liu, Qianqian Chen, Chunxia Li, Jinsong Duan, Kunjie Wang, Jiawei Wang, Bo Sun, Zhonghan Li, Lunzhi Dai, Wei Cheng, Shiqian Qi, Kefeng Lu. The crystal structure of Atg18 reveals a new binding site for Atg2 in Saccharomyces cerevisiae. Cellular and molecular life sciences : CMLS. 2021 Mar;78(5):2131-2143

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PMID: 32809042

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