A ubiquitin-like system mediates protein lipidation

Nature. 2000 Nov 23;408(6811):488-92. doi: 10.1038/35044114.

Abstract

Autophagy is a dynamic membrane phenomenon for bulk protein degradation in the lysosome/vacuole. Apg8/Aut7 is an essential factor for autophagy in yeast. We previously found that the carboxy-terminal arginine of nascent Apg8 is removed by Apg4/Aut2 protease, leaving a glycine residue at the C terminus. Apg8 is then converted to a form (Apg8-X) that is tightly bound to the membrane. Here we report a new mode of protein lipidation. Apg8 is covalently conjugated to phosphatidylethanolamine through an amide bond between the C-terminal glycine and the amino group of phosphatidylethanolamine. This lipidation is mediated by a ubiquitination-like system. Apg8 is a ubiquitin-like protein that is activated by an E1 protein, Apg7 (refs 7, 8), and is transferred subsequently to the E2 enzymes Apg3/Aut1 (ref. 9). Apg7 activates two different ubiquitin-like proteins, Apg12 (ref. 10) and Apg8, and assigns them to specific E2 enzymes, Apg10 (ref. 11) and Apg3, respectively. These reactions are necessary for the formation of Apg8-phosphatidylethanolamine. This lipidation has an essential role in membrane dynamics during autophagy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Autophagy
  • Autophagy-Related Protein 12
  • Autophagy-Related Protein 7
  • Autophagy-Related Protein 8 Family
  • Autophagy-Related Proteins
  • Binding Sites
  • Cell Membrane / metabolism
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism*
  • Molecular Sequence Data
  • Phosphatidylethanolamines / metabolism
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins*
  • Ubiquitin-Conjugating Enzymes
  • Ubiquitins / metabolism*

Substances

  • ATG12 protein, S cerevisiae
  • ATG7 protein, S cerevisiae
  • ATG8 protein, S cerevisiae
  • Autophagy-Related Protein 12
  • Autophagy-Related Protein 8 Family
  • Autophagy-Related Proteins
  • Fungal Proteins
  • Microtubule-Associated Proteins
  • Phosphatidylethanolamines
  • Saccharomyces cerevisiae Proteins
  • Ubiquitins
  • Ubiquitin-Conjugating Enzymes
  • Autophagy-Related Protein 7
  • ATG3 protein, S cerevisiae