Subnanometer resolution cryo-EM structure of Arabidopsis thaliana ATG9
Subnanometer resolution cryo-EM structure of Arabidopsis thaliana ATG9
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拟南芥 ATG9 的亚纳米分辨率冷冻电镜结构
DOI：
10.1080/15548627.2019.1639300
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发表时间：
2019-07-14
期刊：
影响因子：
13.3
通讯作者：
Lau, Wilson Chun Yu
中科院分区：
文献类型：
--
作者：
Lai, Louis Tung Faat;Yu, Chuanyang;Lau, Wilson Chun Yu
巨自噬/自噬是在正常和应激条件下通过回收大分子来维持细胞稳态的重要过程。 ATG9（自噬相关9）是自噬核心机制中唯一的整合膜蛋白，在介导自噬体形成中发挥核心作用。在细胞中，ATG9 存在于移动囊泡上，这些囊泡运输至生长中的吞噬细胞，为自噬体的形成提供重要的膜来源。在这里，我们报告了拟南芥 ATG9 的三维结构，分辨率为 7.8 埃，由单粒子冷冻电子显微镜测定。 ATG9 组织成同源三聚体，每个原聚体贡献至少六个跨膜 α 螺旋。在三聚体的中心，原聚体通过其膜嵌入区域和 C 末端细胞质区域相互作用。结合使用序列共进化信息预测蛋白质接触，该结构提供了对 ATG9 结构的分子见解，并为 ATG9 调节的自噬进展的分子机制提供了可检验的假设。
Macroautophagy/autophagy is an essential process for the maintenance of cellular homeostasis by recycling macromolecules under normal and stress conditions. ATG9 (autophagy related 9) is the only integral membrane protein in the autophagy core machinery and has a central role in mediating autophagosome formation. In cells, ATG9 exists on mobile vesicles that traffic to the growing phagophore, providing an essential membrane source for the formation of autophagosomes. Here we report the three-dimensional structure of ATG9 from Arabidopsis thaliana at 7.8 angstrom resolution, determined by single particle cryo-electron microscopy. ATG9 organizes into a homotrimer, with each protomer contributing at least six transmembrane alpha-helices. At the center of the trimer, the protomers interact via their membrane-embedded and C-terminal cytoplasmic regions. Combined with prediction of protein contacts using sequence co-evolutionary information, the structure provides molecular insights into the ATG9 architecture and testable hypotheses for the molecular mechanism of autophagy progression regulated by ATG9.