Suzuki Nobuo N, Yoshimoto Kohki, Fujioka Yuko, Ohsumi Yoshinori, Inagaki Fuyuhiko
Department of Structural Biology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-ku, Sapporo, Japan.
Autophagy. 2005 Jul;1(2):119-26. doi: 10.4161/auto.1.2.1859. Epub 2005 Jul 23.
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) ATG12 at 1.8 A 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.
Atg12是一种翻译后修饰因子，通过类泛素化缀合系统被激活并与其单一靶标Atg5缀合。Atg12-Atg5缀合物对于自噬至关重要，自噬是液泡/溶酶体系统对细胞质成分进行大量降解的过程。在此，我们证明Atg12缀合系统存在于拟南芥中，并且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（At）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的结构显示出一种泛素折叠，与Atg8的哺乳动物同源物的泛素折叠惊人地相似，Atg8是另一种对自噬必不可少的类泛素修饰因子，它与磷脂酰乙醇胺缀合。AtATG12表面存在两种类型的疏水补丁：一种在Atg12和Atg8直系同源物中都保守，而另一种是Atg12直系同源物特有的。考虑到它们共享Atg7作为类E1酶，我们认为第一个疏水补丁负责缀合反应，而后者参与Atg12的特定功能。
