Structural Basis of the Autophagy-Related LC3/Atg13 LIR Complex: Recognition and Interaction Mechanism
Copyright policy )Structural Basis of the Autophagy-Related LC3/Atg13 LIR Complex: Recognition and Interaction Mechanism
Autophagy is a bulk degradation pathway that removes cytosolic materials to maintain cellular homeostasis. The autophagy-related gene 13 (Atg13) and microtubule associate protein 1 light chain 3 (LC3) proteins are required for autophagosome formation. We demonstrate that each of the human LC3 isoforms (LC3A, LC3B, and LC3C) interacts with Atg13 via the LC3 interacting region (LIR) of Atg13. Using X-ray crystallography, we solved the macromolecular structures of LC3A and LC3C, along with the complex structures of the LC3 isoforms with the Atg13 LIR. Together, our structural and binding analyses reveal that the side-chain of Lys49 of LC3 acts as a gatekeeper to regulate binding of the LIR. We verified this observation by mutation of Lys49 in LC3A, which significantly reduces LC3A positive puncta formation in cultured cells. Our results suggest that specific affinity of the LC3 isoforms to the Atg13 LIR is required for proper autophagosome formation.
- University of Melbourne Australia
- High Energy Accelerator Research Organization Japan
- Stanford University United States
- Osaka University Japan
- SLAC National Accelerator Laboratory United States
Models, Molecular, Binding Sites, Lysine, Molecular Sequence Data, Autophagy-Related Proteins, Fibroblasts, Crystallography, X-Ray, Mice, HEK293 Cells, Gene Expression Regulation, Structural Biology, Phagosomes, Mutation, Autophagy, Escherichia coli, Animals, Humans, Amino Acid Sequence, Molecular Biology, Microtubule-Associated Proteins, Adaptor Proteins, Signal Transducing, Protein Binding
Models, Molecular, Binding Sites, Lysine, Molecular Sequence Data, Autophagy-Related Proteins, Fibroblasts, Crystallography, X-Ray, Mice, HEK293 Cells, Gene Expression Regulation, Structural Biology, Phagosomes, Mutation, Autophagy, Escherichia coli, Animals, Humans, Amino Acid Sequence, Molecular Biology, Microtubule-Associated Proteins, Adaptor Proteins, Signal Transducing, Protein Binding
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