School of Biological and Medical Engineering, Hefei University of Technology, Anhui, Hefei 230009, China.
Tsinghua-Peking Center for Life Sciences, Key Laboratory of Bioorganic Phosphorus Chemistry &Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084, China.
Nat Commun. 2017 Mar 22;8:14846. doi: 10.1038/ncomms14846.
Acetylation of Atg3 regulates the lipidation of the protein Atg8 in autophagy. The molecular mechanism behind this important biochemical event remains to be elucidated. We describe the first semi-synthesis of homogeneous K19/K48-diacetylated Atg3 through sequential hydrazide-based native chemical ligation. In vitro reconstitution experiments with the semi-synthetic proteins confirm that Atg3 acetylation can promote the lipidation of Atg8. We find that acetylation of Atg3 enhances its binding to phosphatidylethanolamine-containing liposomes and to endoplasmic reticulum, through which it promotes the lipidation process.
乙酰化 Atg3 调节自噬中蛋白质 Atg8 的脂质化。这一重要生化事件背后的分子机制仍有待阐明。我们通过顺序基于酰肼的天然化学连接描述了均匀的 K19/K48-二乙酰化 Atg3 的首次半合成。半合成蛋白的体外重建实验证实，Atg3 乙酰化可以促进 Atg8 的脂质化。我们发现，Atg3 的乙酰化增强了其与含有磷脂酰乙醇胺的脂质体和内质网的结合，从而促进了脂质化过程。
