饥饿诱导自噬起始复合物组装的结构基础。
Structural basis of starvation-induced assembly of the autophagy initiation complex.
机构信息
1] Institute of Microbial Chemistry (BIKAKEN), Tokyo, Japan. [2].
1] Frontier Research Center, Tokyo Institute of Technology, Yokohama, Japan. [2] Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama, Japan. [3].
出版信息
Nat Struct Mol Biol. 2014 Jun;21(6):513-21. doi: 10.1038/nsmb.2822. Epub 2014 May 4.
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.
组装前自噬体结构 (PAS) 对于酵母中自噬的起始是必不可少的。饥饿诱导的 Atg13 去磷酸化对于 Atg1-Atg13-Atg17-Atg29-Atg31 复合物（Atg1 复合物）的形成是必需的，这是 PAS 组装的前提。然而，这些事件背后的分子细节尚未确定。在这里，我们通过 X 射线晶体学研究了酵母 Atg13 与 Atg1 和 Atg17 的相互作用。Atg13 使用一个伸长的螺旋-环-螺旋区域与 Atg1 中的串联微管相互作用和运输结构域结合。Atg13 还与 Atg17 结合，使用一个短区域，从而桥接 Atg1 和 Atg17 并导致 Atg1 复合物的形成。Atg13 中特定丝氨酸的去磷酸化不仅增强了其与 Atg1 的相互作用，也增强了与 Atg17 的相互作用。这些观察结果更新了自噬起始模型如下：在饥饿时，去磷酸化的 Atg13 与 Atg1 和 Atg17 都结合，这促进了 PAS 组装和自噬的进展。
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