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

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 E1 enzyme for Atg8, and it activates the C-terminal Gly116 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 β-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 α-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.
Mesh Terms:
Adenosine Triphosphate, Autophagy-Related Protein 7, Autophagy-Related Protein 8 Family, Crystallography, X-Ray, Models, Molecular, Protein Binding, Protein Conformation, Protein Interaction Domains and Motifs, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins
J. Mol. Biol.
Date: Dec. 02, 2017
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