Atg7 Activates an Autophagy-Essential Ubiquitin-like Protein Atg8 through Multi-Step Recognition

作者：Yamaguchi Masaya; Satoo Kenji; Suzuki Hironori; Fujioka Yuko; Ohsumi Yoshinori; Inagaki Fuyuhiko; Noda Nobuo N^*

来源：Journal of Molecular Biology, 2018, 430(3): 249-257.

DOI：10.1016/j.jmb.2017.12.002

• autophagy
• Atg7
• Atg8
• E1
• crystal structure

Atg8 is a unique ubiquitin-like protein that is covalently conjugated with a phosphatidylethanolamine through reactions similar to ubiquitination and plays essential roles in autophagy. Atg7 is the El enzyme for Atg8, and it activates the C-terminal Glyl 16 of Atg8 using ATP. Here, we report the crystal structure of Atg8 bound to the C-terminal domain of Atg7 in an unprecedented mode. Atg8 neither contacts with the central beta-sheet nor binds to the catalytic site of Atg7, both of which were observed in previously reported Atg7 Atg8 structures. Instead, Atg8 binds to the C-terminal a-helix and crossover loop, thereby changing the autoinhibited conformation of the crossover loop observed in the free Atg7 structure into a short helix and a disordered loop. Mutational analyses suggested that this interaction mode is important for the activation reaction. We propose that Atg7 recognizes Atg8 through multiple steps, which would be necessary to induce a conformational change in Atg7 that is optimal for the activation reaction.

• 出版日期2018-2-2