Structural basis of FYCO1 and MAP1LC3A interaction reveals a novel binding mode for Atg8-family proteins
Structural basis of FYCO1 and MAP1LC3A interaction reveals a novel binding mode for Atg8-family proteins
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FYCO1 和 MAP1LC3A 相互作用的结构基础揭示了 Atg8 家族蛋白的新型结合模式。
DOI：
10.1080/15548627.2016.1185590
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发表时间：
2016-01-01
期刊：
影响因子：
13.3
通讯作者：
Pan, Lifeng
中科院分区：
文献类型：
--
作者：
Cheng, Xiaofang;Wang, Yingli;Pan, Lifeng
FYCO 1（FYVE and coiled-coil domain containing 1，FYCO 1）作为一种自噬适配器，直接连接自噬体和微管驱动蛋白马达，在微管和自噬囊泡的末端定向转运中发挥重要作用。FYCO 1与自噬体的特异性结合是通过其与自噬体外表面修饰的Atg 8家族蛋白的相互作用介导的。然而，FYCO 1和Atg 8家族蛋白之间相互作用的机制基础在很大程度上是未知的。在这里，使用生物化学和结构分析，我们证明了FYCO 1含有一个独特的LC 3相互作用区（LIR），它区别性地结合哺乳动物Atg 8直系同源物，并优先结合MAP 1 LC 3A和MAP 1 LC 3B。除了揭示FYCO 1 LIR和MAP 1 LC 3A相互作用的详细分子机制外，确定的FYCO 1-LIR-MAP 1 LC 3A复合物结构还揭示了Atg 8家族蛋白的独特LIR结合模式，并首先证明了LIR核心基序C端相邻序列与Atg 8家族蛋白结合的功能相关性。总之，我们的研究结果不仅为FYCO 1介导的自噬体转运提供了新的机制见解，而且还扩展了我们对LIR基序和Atg 8家族蛋白之间相互作用模式的理解。
FYCO1 (FYVE and coiled-coil domain containing 1) functions as an autophagy adaptor in directly linking autophagosomes with the microtubule-based kinesin motor, and plays an essential role in the microtubule plus end-directed transport of autophagic vesicles. The specific association of FYCO1 with autophagosomes is mediated by its interaction with Atg8-family proteins decorated on the outer surface of autophagosome. However, the mechanistic basis governing the interaction between FYCO1 and Atg8-family proteins is largely unknown. Here, using biochemical and structural analyses, we demonstrated that FYCO1 contains a unique LC3-interacting region (LIR), which discriminately binds to mammalian Atg8 orthologs and preferentially binds to the MAP1LC3A and MAP1LC3B. In addition to uncovering the detailed molecular mechanism underlying the FYCO1 LIR and MAP1LC3A interaction, the determined FYCO1-LIR-MAP1LC3A complex structure also reveals a unique LIR binding mode for Atg8-family proteins, and demonstrates, first, the functional relevance of adjacent sequences C-terminal to the LIR core motif for binding to Atg8-family proteins. Taken together, our findings not only provide new mechanistic insight into FYCO1-mediated transport of autophagosomes, but also expand our understanding of the interaction modes between LIR motifs and Atg8-family proteins in general.