Lipidation of the LC3/GABARAP family of autophagy proteins relies on a membrane-curvature-sensing domain in Atg3
| Autor: | Wendy M. Fong, Thomas J. Melia, Julia Dancourt, Ai Yamamoto, Sangeeta Nath, Gabriella Puente, Joerg Bewersdorf, Bruno Antonny, Vladimir Shteyn, Shanta Nag |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Autophagosome
ATG8 Autophagosome maturation GABARAP Amino Acid Motifs Autophagy-Related Proteins Lipid-anchored protein Ubiquitin-Activating Enzymes Biology Transfection Autophagy-Related Protein 7 Article 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Stress Physiological LC3 Animals Humans 030304 developmental biology Adaptor Proteins Signal Transducing Phosphatidylethanolamine Mice Knockout 0303 health sciences Curvature Phosphatidylethanolamines Autophagy Cell Membrane Microfilament Proteins Membrane Proteins Cell Biology Autophagy-Related Protein 8 Family Cell biology Rats GABARAP-L1 Cytoskeletal Proteins chemistry Membrane curvature Liposomes Mutation Ubiquitin-Conjugating Enzymes Atg3 Apoptosis Regulatory Proteins Hydrophobic and Hydrophilic Interactions Microtubule-Associated Proteins 030217 neurology & neurosurgery HeLa Cells Signal Transduction |
| Zdroj: | Nature cell biology |
| ISSN: | 1476-4679 |
| Popis: | The protein biochemistry supporting autophagosome growth on the cup-like isolation membrane is likely different from the biochemistry on the closed and maturing autophagosome. Thus, the highly curved rim of the cup may serve as a functionally-required surface for transiently-associated components of the early-acting autophagic machinery. Here we demonstrate that the E2-like enzyme, Atg3, facilitates LC3/GABARAPlipidation only on membranes exhibiting local lipid-packing defects. This activity requires an amino-terminal amphipathic helix similar to motifs found on proteins targeting highly curved intracellular membranes. By tuning the hydrophobicity of this motif, we can promote or inhibit lipidation in vitro and in rescue experiments in Atg3 knockout cells, implying a physiologic role for this stress detection. The need for extensive lipid-packing defects suggests that Atg3 is designed to work at highly-curved membranes perhaps including the limiting edge of the growing phagophore. |
| Databáze: | OpenAIRE |
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