Structural basis of starvation-induced assembly of the autophagy initiation complex
Structural basis of starvation-induced assembly of the autophagy initiation complex
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DOI：
10.1038/nsmb.2822
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发表时间：
2014-06-01
影响因子：
16.8
通讯作者：
Noda, Nobuo N.
中科院分区：
文献类型：
--
作者：
Fujioka, Yuko;Suzuki, Sho W.;Noda, Nobuo N.
自噬体前结构（pre - autophagosomal structure， PAS）的组装是酵母自噬起始的必要条件。饥饿诱导的Atg13去磷酸化是Atg1-Atg13- atg17 - atg29 - atg31复合物（Atg1复合物）形成所必需的，Atg1复合物是PAS组装的先决条件。然而，这些事件背后的分子细节尚未确定。本文利用x射线晶体学研究了酵母Atg13与Atg1和Atg17的相互作用。Atg13通过细长的螺旋-环-螺旋区域结合串联微管相互作用和Atg1中的转运结构域。Atg13也通过一个短区域结合Atg17，从而桥接Atg1和Atg17，导致Atg1复合物的形成。Atg13中特定丝氨酸的去磷酸化不仅增强了它与Atg1的相互作用，也增强了它与Atg17的相互作用。这些观察结果更新了自噬启动模型如下：饥饿时，去磷酸化的Atg13结合Atg1和Atg17，这促进了PAS组装和自噬进程。
Assembly of the preautophagosomal structure (PAS) is essential for autophagy initiation in yeast. Starvation-induced dephosphorylation of Atg13 is required for the formation of the Atg1-Atg13-Atg17-Atg29-Atg31 complex (Atg1 complex), a prerequisite for PAS assembly. However, molecular details underlying these events have not been established. Here we studied the interactions of yeast Atg13 with Atg1 and Atg17 by X-ray crystallography. Atg13 binds tandem microtubule interacting and transport domains in Atg1, using an elongated helix-loop-helix region. Atg13 also binds Atg17, using a short region, thereby bridging Atg1 and Atg17 and leading to Atg1-complex formation. Dephosphorylation of specific serines in Atg13 enhanced its interaction with not only Atg1 but also Atg17. These observations update the autophagy-initiation model as follows: upon starvation, dephosphorylated Atg13 binds both Atg1 and Atg17, and this promotes PAS assembly and autophagy progression.