Structural Basis of the Autophagy-Related LC3/Atg13 LIR Complex: Recognition and Interaction Mechanism
Structural Basis of the Autophagy-Related LC3/Atg13 LIR Complex: Recognition and Interaction Mechanism
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DOI：
10.1016/j.str.2013.09.023
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发表时间：
2014-01-07
期刊：
影响因子：
5.7
通讯作者：
Wakatsuki, Soichi
中科院分区：
文献类型：
--
作者：
Suzuki, Hironori;Tabata, Keisuke;Wakatsuki, Soichi
自噬是一种清除胞质物质以维持细胞内稳态的大量降解途径。自噬相关基因13（Atg 13）和微管相关蛋白1轻链3（LC 3）蛋白是自噬体形成所必需的。我们证明，每个人的LC 3亚型（LC 3A，LC 3B，和LC 3C）与Atg 13通过LC 3相互作用区（LIR）的Atg 13相互作用。使用X-射线晶体学，我们解决了LC 3A和LC 3C的大分子结构，沿着的LC 3异构体与Atg 13 LIR的复杂结构。总之，我们的结构和结合分析表明，LC 3的Lys 49侧链作为看门人，以调节LIR的结合。我们通过LC 3A中Lys 49的突变验证了这一观察结果，这显著减少了培养细胞中LC 3A阳性斑点的形成。我们的研究结果表明，特定的亲和力的LC 3亚型的Atg 13 LIR所需的适当的自噬体的形成。
Autophagy is a bulk degradation pathway that removes cytosolic materials to maintain cellular homeostasis. The autophagy-related gene 13 (Atg13) and microtubule associate protein 1 light chain 3 (LC3) proteins are required for autophagosome formation. We demonstrate that each of the human LC3 isoforms (LC3A, LC3B, and LC3C) interacts with Atg13 via the LC3 interacting region (LIR) of Atg13. Using X-ray crystallography, we solved the macromolecular structures of LC3A and LC3C, along with the complex structures of the LC3 isoforms with the Atg13 LIR. Together, our structural and binding analyses reveal that the side-chain of Lys49 of LC3 acts as a gatekeeper to regulate binding of the LIR. We verified this observation by mutation of Lys49 in LC3A, which significantly reduces LC3A positive puncta formation in cultured cells. Our results suggest that specific affinity of the LC3 isoforms to the Atg13 LIR is required for proper autophagosome formation.