The crystal structure of Atg3, an autophagy-related ubiquitin carrier protein (E2) enzyme that mediates Atg8 lipidation
The crystal structure of Atg3, an autophagy-related ubiquitin carrier protein (E2) enzyme that mediates Atg8 lipidation
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DOI：
10.1074/jbc.m611473200
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发表时间：
2007-03-16
影响因子：
4.8
通讯作者：
Inagaki, Fuyuhiko
中科院分区：
文献类型：
--
作者：
Yamada, Yuya;Suzuki, Nobuo N.;Inagaki, Fuyuhiko
Atg 3是一种E2样酶，催化Atg 8和磷脂酰乙醇胺（PE）的结合。Atg 8-PE缀合物对于自噬是必不可少的，自噬是细胞质组分通过液泡/溶酶体系统的大量降解过程。我们在这里报告的晶体结构的酿酒酵母Atg 3在2.5埃分辨率。Atg 3具有α/β折叠，其核心区域在拓扑学上类似于典型的E2酶。Atg 3在核心区有两个插入区域，其中一个由近似80个残基组成，在溶液中具有无规卷曲结构，另一个具有长α-螺旋结构，从核心区突出30埃。在体内和体外分析表明，前一个区域是负责结合Atg 7，E1样酶，后者是负责结合Atg 8。一个硫酸根离子附近的催化半胱氨酸的Atg 3结合，这表明一个可能的结合位点的磷酸部分的PE。Atg 3的结构为理解Atg 3进行的独特脂化反应提供了分子基础。
Atg3 is an E2-like enzyme that catalyzes the conjugation of Atg8 and phosphatidylethanolamine (PE). The Atg8-PE conjugate is essential for autophagy, which is the bulk degradation process of cytoplasmic components by the vacuolar/lysosomal system. We report here the crystal structure of Saccharomyces cerevisiae Atg3 at 2.5-angstrom resolution. Atg3 has an alpha/beta-fold, and its core region is topologically similar to canonical E2 enzymes. Atg3 has two regions inserted in the core region, one of which consists of similar to 80 residues and has a random coil structure in solution and another with a long a-helical structure that protrudes from the core region as far as 30 angstrom. In vivo and in vitro analyses suggested that the former region is responsible for binding Atg7, an E1-like enzyme, and that the latter is responsible for binding Atg8. A sulfate ion was bound near the catalytic cysteine of Atg3, suggesting a possible binding site for the phosphate moiety of PE. The structure of Atg3 provides a molecular basis for understanding the unique lipidation reaction that Atg3 carries out.