Structural Basis of Atg8 Activation by a Homodimeric E1, Atg7
Copyright policy )Structural Basis of Atg8 Activation by a Homodimeric E1, Atg7
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.
- Institute of Science Tokyo Japan
- Hokkaido Bunkyo University Japan
- Hokkaido University Japan
Models, Molecular, Binding Sites, Saccharomyces cerevisiae Proteins, Time Factors, Protein Conformation, Recombinant Fusion Proteins, Autophagy-Related Proteins, Cell Biology, Autophagy-Related Protein 8 Family, Crystallography, X-Ray, Autophagy-Related Protein 7, Enzyme Activation, Structure-Activity Relationship, Adenosine Triphosphate, Multienzyme Complexes, Mutation, Protein Interaction Mapping, Ubiquitin-Conjugating Enzymes, Protein Interaction Domains and Motifs, Protein Multimerization, Molecular Biology, Microtubule-Associated Proteins
Models, Molecular, Binding Sites, Saccharomyces cerevisiae Proteins, Time Factors, Protein Conformation, Recombinant Fusion Proteins, Autophagy-Related Proteins, Cell Biology, Autophagy-Related Protein 8 Family, Crystallography, X-Ray, Autophagy-Related Protein 7, Enzyme Activation, Structure-Activity Relationship, Adenosine Triphosphate, Multienzyme Complexes, Mutation, Protein Interaction Mapping, Ubiquitin-Conjugating Enzymes, Protein Interaction Domains and Motifs, Protein Multimerization, Molecular Biology, Microtubule-Associated Proteins
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