The amino-terminal region of Atg3 is essential for association with phosphatidylethanolamine in Atg8 lipidation

FEBS Lett. 2009 Apr 2;583(7):1078-83. doi: 10.1016/j.febslet.2009.03.009. Epub 2009 Mar 13.

Abstract

Autophagy is a bulk degradation process conserved among eukaryotes. In macro-autophagy, autophagosomes sequester cytoplasmic components and deliver their contents to lysosomes/vacuoles. Autophagosome formation requires the conjugation of Atg8, a ubiquitin-like protein, to phosphatidylethanolamine (PE). Here we report that the amino (N)-terminal region of Atg3, an E2-like enzyme for Atg8, plays a crucial role in Atg8-PE conjugation. The conjugating activities of Atg3 mutants lacking the 7 N-terminal amino acid residues or containing a Leu-to-Asp mutation at position 6 were severely impaired both in vivo and in vitro. In addition, the amino-terminal region is critical for interaction with the substrate, PE.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autophagy / physiology*
  • Autophagy-Related Protein 8 Family
  • Autophagy-Related Proteins
  • Lysosomes / genetics
  • Lysosomes / metabolism*
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism*
  • Phosphatidylethanolamines / genetics
  • Phosphatidylethanolamines / metabolism*
  • Protein Structure, Tertiary / physiology
  • Saccharomyces cerevisiae / cytology
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Ubiquitin / genetics
  • Ubiquitin / metabolism
  • Ubiquitin-Conjugating Enzymes / genetics
  • Ubiquitin-Conjugating Enzymes / metabolism*
  • Vacuoles / genetics
  • Vacuoles / metabolism

Substances

  • ATG8 protein, S cerevisiae
  • Autophagy-Related Protein 8 Family
  • Autophagy-Related Proteins
  • Microtubule-Associated Proteins
  • Phosphatidylethanolamines
  • Saccharomyces cerevisiae Proteins
  • Ubiquitin
  • phosphatidylethanolamine
  • Ubiquitin-Conjugating Enzymes
  • ATG3 protein, S cerevisiae