A semisynthetic Atg3 reveals that acetylation promotes Atg3 membrane binding and Atg8 lipidation

Nat Commun. 2017 Mar 22:8:14846. doi: 10.1038/ncomms14846.

Abstract

Acetylation of Atg3 regulates the lipidation of the protein Atg8 in autophagy. The molecular mechanism behind this important biochemical event remains to be elucidated. We describe the first semi-synthesis of homogeneous K19/K48-diacetylated Atg3 through sequential hydrazide-based native chemical ligation. In vitro reconstitution experiments with the semi-synthetic proteins confirm that Atg3 acetylation can promote the lipidation of Atg8. We find that acetylation of Atg3 enhances its binding to phosphatidylethanolamine-containing liposomes and to endoplasmic reticulum, through which it promotes the lipidation process.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Amino Acid Sequence
  • Autophagy-Related Protein 8 Family / metabolism*
  • Autophagy-Related Proteins / chemistry
  • Autophagy-Related Proteins / metabolism*
  • Endoplasmic Reticulum / metabolism
  • Esters / metabolism
  • Intracellular Membranes / metabolism*
  • Lipids / chemistry*
  • Liposomes
  • Lysine / metabolism
  • Models, Biological
  • Protein Binding
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Ubiquitin-Conjugating Enzymes / chemistry
  • Ubiquitin-Conjugating Enzymes / metabolism*

Substances

  • ATG8 protein, S cerevisiae
  • Autophagy-Related Protein 8 Family
  • Autophagy-Related Proteins
  • Esters
  • Lipids
  • Liposomes
  • Saccharomyces cerevisiae Proteins
  • Ubiquitin-Conjugating Enzymes
  • ATG3 protein, S cerevisiae
  • Lysine