A ubiquitin-like system mediates protein lipidation
A ubiquitin-like system mediates protein lipidation
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DOI：
10.1038/35044114
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发表时间：
2000-11-23
期刊：
影响因子：
64.8
通讯作者：
Ohsumi, Y
中科院分区：
文献类型：
--
作者：
Ichimura, Y;Kirisako, T;Ohsumi, Y
自噬是溶酶体/液泡中大量蛋白质降解的动态膜现象（1，2）。Apg 8/Aut 7是酵母中自噬的重要因子（3-5）。我们之前发现新生Apg 8的羧基末端精氨酸被Apg 4/Aut 2蛋白酶去除，在C末端留下甘氨酸残基（6）。Apg 8然后转化为与膜紧密结合的形式（Apg 8-X）（6）。在这里，我们报告了一种新的蛋白质脂化模式。Apg 8通过磷脂酰乙醇胺的C-末端甘氨酸和氨基之间的酰胺键与磷脂酰乙醇胺共价结合。这种脂化是由一个泛素化样系统介导的。Apg 8是一种泛素样蛋白，由E1蛋白Apg 7激活（参考文献7，8），随后转移至E2酶Apg 3/Aut 1（参考文献9）。Apg 7激活两种不同的泛素样蛋白Apg 12（参考文献10）和Apg 8，并将它们分别分配给特定的E2酶Apg 10（参考文献11）和Apg 3。这些反应对于Apg 8-磷脂酰乙醇胺的形成是必需的。这种脂化在自噬过程中的膜动力学中起着重要作用（6）。
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(3-5). 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).