A ubiquitin-like system mediates protein lipidation

• Published in: Nature (London) Vol. 408; no. 6811; pp. 488 - 492
• Main Authors: Ichimura, Yoshinobu, Kirisako, Takayoshi, Takao, Toshifumi, Satomi, Yoshinori, Shimonishi, Yasutsugu, Ishihara, Naotada, Mizushima, Noboru, Tanida, Isei, Kominami, Eiki, Ohsumi, Mariko, Noda, Takeshi, Ohsumi, Yoshinori
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 23.11.2000; Nature Publishing; Nature Publishing Group
• Subjects: Amino Acid Sequence; Apg10 protein; Apg12 protein; Apg3 protein; Apg7 protein; Apg8 protein; Aut1 protein; Aut7 protein; Autophagy; Autophagy-Related Protein 12; Autophagy-Related Protein 7; Autophagy-Related Protein 8 Family; Autophagy-Related Proteins; Binding Sites; Biodegradation; Biological and medical sciences; Cell Membrane - metabolism; Cellular biology; Conformational dynamics in molecular biology; Enzymes; Fundamental and applied biological sciences. Psychology; Fungal Proteins - genetics; Fungal Proteins - metabolism; Humanities and Social Sciences; letter; Lipids; Membranes; Microtubule-Associated Proteins - genetics; Microtubule-Associated Proteins - metabolism; Molecular biophysics; Molecular Sequence Data; Molecules; multidisciplinary; phosphatidylethanolamine; Phosphatidylethanolamines - metabolism; Proteins; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae Proteins; Science; Science (multidisciplinary); ubiquitin; Ubiquitin-Conjugating Enzymes; Ubiquitins - metabolism; Yeasts; Fungi; Ubiquitin; Phosphatidylethanolamine; Conformational dynamics; Ascomycetes; Biomembrane; Saccharomyces cerevisiae; Protein; Thallophyta
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/35044114

Autophagy is a dynamic membrane phenomenon for bulk protein degradation in the lysosome/vacuole 1 , 2 . Apg8/Aut7 is an essential factor for autophagy in yeast 3 , 4 , 5 . 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 6 . Apg8 is then converted to a form (Apg8-X) that is tightly bound to the membrane 6 . 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 6 .