The crystal structure of plant ATG12 and its biological implication in autophagy
The crystal structure of plant ATG12 and its biological implication in autophagy
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DOI：
10.4161/auto.1.2.1859
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发表时间：
2005-07-01
期刊：
影响因子：
13.3
通讯作者：
Inagaki, Fuyuhiko
中科院分区：
文献类型：
--
作者：
Suzuki, Nobuo N.;Yoshimoto, Kohki;Inagaki, Fuyuhiko
ATG12是一种翻译后修饰物，通过类似泛素的连接系统激活并与其单一靶点ATG5结合。ATG12-ATG5结合物对于自噬是必不可少的，自噬是由空泡/溶酶体系统大量降解细胞质成分的过程。在这里，我们证明了Atg12结合系统存在于拟南芥中，对于植物自噬以及在酵母和哺乳动物中都是必不可少的。我们还报道了拟南芥ATG12在1.8埃分辨率下的晶体结构。尽管与泛素没有明显的序列同源性，但AtATG12的结构显示出与哺乳动物ATG8同源物的泛素折叠，Atg8是另一种与磷脂酰乙醇胺偶联的自噬必需的泛素样修饰物。AtATG12表面存在两种类型的疏水斑块：一种在Atg12和Atg8同源基因中都保守，另一种是Atg12同源基因所独有的。考虑到它们都是作为一种E1样酶的ATG7，我们认为第一个疏水斑块负责接合反应，而后者参与ATG12的特异性功能。
Atg12 is a post-translational modifier that is activated and conjugated to its single target, Atg5, by a ubiquitin-like conjugation system. The Atg12-Atg5 conjugate is essential for autophagy, the bulk degradation process of cytoplasmic components by the vacuolar/lysosomal system. Here, we demonstrate that the Atg12 conjugation system exists in Arabidopsis and is essential for plant autophagy as well as in yeast and mammals. We also report the crystal structure of Arabidopsis thaliana (At) ATG 12 at 1.8 angstrom resolution. Despite no obvious sequence homology with ubiquitin, the structure of AtATG12 shows a ubiquitin fold strikingly similar to those of mammalian homologs of Atg8, the other ubiquitin-like modifier essential for autophagy, which is conjugated to phosphatidylethanolamine. Two types of hydrophobic patches are present on the surface of AtATG12: one is conserved in both Atg12 and Atg8 orthologs, while the other is unique to Atg12 orthologs. Considering that they share Atg7 as an E1-like enzyme, we suggest that the first hydrophobic patch is responsible for the conjugation reaction, while the latter is involved in Atg12-specific functions.