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Nat Cell Biol. 2014 May;16(5):415-24. doi: 10.1038/ncb2940. Epub 2014 Apr 20.

Lipidation of the LC3/GABARAP family of autophagy proteins relies on a membrane-curvature-sensing domain in Atg3.

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1] Department of Cell Biology, Yale University School of Medicine, New Haven, Connecticut 06510, USA [2].
Department of Cell Biology, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
Departments of Neurology, Pathology and Cell Biology, Columbia University, New York 10032, USA.
Institut de Pharmacologie Moléculaire et Cellulaire, CNRS et université de Nice, 06103, France.

Erratum in

  • Nat Cell Biol. 2014 Aug;16(8):821.
  • Nat Cell Biol. 2014 Jul;16(7):716.


The components supporting autophagosome growth on the cup-like isolation membrane are likely to be different from those found on closed and maturing autophagosomes. 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/GABARAP lipidation 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.

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