Structural Basis of Atg8 Activation by a Homodimeric E1, Atg7
Structural Basis of Atg8 Activation by a Homodimeric E1, Atg7
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DOI：
10.1016/j.molcel.2011.08.035
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发表时间：
2011-11-04
期刊：
影响因子：
16
通讯作者：
Inagaki, Fuyuhiko
中科院分区：
文献类型：
--
作者：
Noda, Nobuo N.;Satoo, Kenji;Inagaki, Fuyuhiko
E1酶激活泛素样蛋白并将其转移到同源E2酶。Atg 7是一种非经典的E1，激活两种泛素样蛋白Atg 8和Atg 12，并在自噬中起着至关重要的作用。在这里，我们报告的晶体结构的全长Atg 7和它的C-末端结构域绑定到Atg 8和MgATP，以及溶液结构的Atg 8绑定到极端的C-末端结构域（ECTD）的Atg 7。Atg 7的独特N-末端结构域（NTD）负责Atg 3（E2）结合，而其C-末端结构域由同源二聚体腺苷酸化结构域（AD）和ECTD组成。结构和生化数据表明，Atg 8最初被ECTD的C-末端尾识别，然后转移到AD，其中Atg 8 C末端被催化半胱氨酸攻击以形成硫酯键。Atg 8然后通过反式机制转移到与二聚体内的相对原聚体的NTD结合的Atg 3。
E1 enzymes activate ubiquitin-like proteins and transfer them to cognate E2 enzymes. Atg7, a noncanonical E1, activates two ubiquitin-like proteins, Atg8 and Atg12, and plays a crucial role in autophagy. Here, we report crystal structures of full-length Atg7 and its C-terminal domain bound to Atg8 and MgATP, as well as a solution structure of Atg8 bound to the extreme C-terminal domain (ECTD) of Atg7. The unique N-terminal domain (NTD) of Atg7 is responsible for Atg3 (E2) binding, whereas its C-terminal domain is comprised of a homodimeric adenylation domain (AD) and ECTD. The structural and biochemical data demonstrate that Atg8 is initially recognized by the C-terminal tail of ECTD and is then transferred to an AD, where the Atg8 C terminus is attacked by the catalytic cysteine to form a thioester bond. Atg8 is then transferred via a trans mechanism to the Atg3 bound to the NTD of the opposite protomer within a dimer.