A ubiquitin-like system mediates protein lipidation.
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.
Ichimura
Y
Y
Department of Cell Biology, National Institute for Basic Biology, Okazaki, Japan.
Kirisako
T
T
Takao
T
T
Satomi
Y
Y
Shimonishi
Y
Y
Ishihara
N
N
Mizushima
N
N
Tanida
I
I
Kominami
E
E
Ohsumi
M
M
Noda
T
T
Ohsumi
Y
Y
D000595:Amino Acid Sequence; D001343:Autophagy; D000071192:Autophagy-Related Protein 12; D000071193:Autophagy-Related Protein 7; D000071190:Autophagy-Related Protein 8 Family; D000071183:Autophagy-Related Proteins; D001665:Binding Sites; D002462:Cell Membrane / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D010714:Phosphatidylethanolamines / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D044763:Ubiquitin-Conjugating Enzymes; D014452:Ubiquitins / Q000378:metabolism*
C491969:ATG12 protein, S cerevisiae; C114830:ATG7 protein, S cerevisiae; C113757:ATG8 protein, S cerevisiae; D000071192:Autophagy-Related Protein 12; D000071190:Autophagy-Related Protein 8 Family; D000071183:Autophagy-Related Proteins; D005656:Fungal Proteins; D008869:Microtubule-Associated Proteins; D010714:Phosphatidylethanolamines; D029701:Saccharomyces cerevisiae Proteins; D014452:Ubiquitins; D044763:Ubiquitin-Conjugating Enzymes; D000071193:Autophagy-Related Protein 7; C104235:ATG3 protein, S cerevisiae