Mechanism of cargo-directed Atg8 conjugation during selective autophagy
Copyright policy )Mechanism of cargo-directed Atg8 conjugation during selective autophagy
Selective autophagy is mediated by cargo receptors that link the cargo to the isolation membrane via interactions with Atg8 proteins. Atg8 proteins are localized to the membrane in an ubiquitin-like conjugation reaction, but how this conjugation is coupled to the presence of the cargo is unclear. Here we show that the S. cerevisiae Atg19, Atg34 and the human p62, Optineurin and NDP52 cargo receptors interact with the E3-like enzyme Atg12~Atg5-Atg16, which stimulates Atg8 conjugation. The interaction of Atg19 with the Atg12~Atg5-Atg16 complex is mediated by its Atg8-interacting motifs (AIMs). We identify the AIM-binding sites in the Atg5 subunit and mutation of these sites impairs selective autophagy. In a reconstituted system the recruitment of the E3 to the prApe1 cargo is sufficient to drive accumulation of conjugated Atg8 at the cargo. The interaction of the Atg12~Atg5-Atg16 complex and Atg8 with Atg19 is mutually exclusive, which may confer directionality to the system.
- Vienna Biocenter Austria
- Max F. Perutz Laboratories Austria
- University of Vienna Austria
- University of Natural Resources and Life Sciences Austria
106002 Biochemie, UBIQUITIN-LIKE PROTEINS, Autophagy-Related Proteins, Cell Cycle Proteins, Biochemistry, Protein Structure, Secondary, Autophagy-Related Protein 5, SACCHAROMYCES-CEREVISIAE, SWISS-MODEL WORKSPACE, protein conjugation, SCAFFOLD PROTEIN, Biology (General), Cloning, Molecular, IN-VIVO, Q, R, Nuclear Proteins, Molecular Docking Simulation, 106054 Zoologie, Medicine, biochemical reconstitution, Autophagy-Related Protein 12, Protein Binding, STRUCTURAL BASIS, QH301-705.5, ATG12-ATG5 CONJUGATE, Science, LIPIDATION, 106054 Zoology, membrane biology, Autophagy, Escherichia coli, Humans, Protein Interaction Domains and Motifs, Amino Acid Sequence, selective autophagy, Binding Sites, Membrane Transport Proteins, 106002 Biochemistry, Biological Transport, Autophagy-Related Protein 8 Family, Gene Expression Regulation, MOLECULAR-DYNAMICS, cargo receptor, MEMBRANE, HeLa Cells
106002 Biochemie, UBIQUITIN-LIKE PROTEINS, Autophagy-Related Proteins, Cell Cycle Proteins, Biochemistry, Protein Structure, Secondary, Autophagy-Related Protein 5, SACCHAROMYCES-CEREVISIAE, SWISS-MODEL WORKSPACE, protein conjugation, SCAFFOLD PROTEIN, Biology (General), Cloning, Molecular, IN-VIVO, Q, R, Nuclear Proteins, Molecular Docking Simulation, 106054 Zoologie, Medicine, biochemical reconstitution, Autophagy-Related Protein 12, Protein Binding, STRUCTURAL BASIS, QH301-705.5, ATG12-ATG5 CONJUGATE, Science, LIPIDATION, 106054 Zoology, membrane biology, Autophagy, Escherichia coli, Humans, Protein Interaction Domains and Motifs, Amino Acid Sequence, selective autophagy, Binding Sites, Membrane Transport Proteins, 106002 Biochemistry, Biological Transport, Autophagy-Related Protein 8 Family, Gene Expression Regulation, MOLECULAR-DYNAMICS, cargo receptor, MEMBRANE, HeLa Cells
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