Lipidation of Atg8: how is substrate specificity determined without a canonical E3 enzyme?
Atg8 and its mammalian homolog LC3, ubiquitin-like proteins (Ubls) required for autophagosome formation, are remarkably unique in that their conjugation target is the lipid phosphatidylethanolamine (PE). Although PE was identified as the sole lipid conjugated with Atg8/LC3 in vivo, phosphatidylserine (PS) can be also a good substrate for its conjugation reaction in vitro. This posed a simple, intriguing question: What confers substrate specificity to lipidation of Atg8/LC3 in vivo? Our recent in vitro studies propose that intracellular milieus such as cytosolic pH and acidic phospholipids in membranes significantly contribute to selective production of the Atg8-PE conjugate.
Nakatogawa
Hitoshi
H
Department of Cell Biology, National Institute for Basic Biology, Okazaki, Japan.
Oh-oka
Kyoko
K
Ohsumi
Yoshinori
Y
D000071190:Autophagy-Related Protein 8 Family; D006863:Hydrogen-Ion Concentration; D008869:Microtubule-Associated Proteins / Q000737:chemistry*; D010714:Phosphatidylethanolamines / Q000737:chemistry*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry*; D013379:Substrate Specificity; D044767:Ubiquitin-Protein Ligases / Q000737:chemistry
C113757:ATG8 protein, S cerevisiae; D000071190:Autophagy-Related Protein 8 Family; D008869:Microtubule-Associated Proteins; D010714:Phosphatidylethanolamines; D029701:Saccharomyces cerevisiae Proteins; C483858:phosphatidylethanolamine; D044767:Ubiquitin-Protein Ligases