ABSTRACT

The Atg3 protein is highly homologous from yeast to human. Atg3 functions as an E2-like enzyme promoting conjugation of Atg8-family proteins to phosphatidylethanolamine (PE), a lipid molecule embedded in the growing phagophore membrane during stress-induced autophagy. Over the last decade, Atg3 became one of the most explored autophagy proteins, resulting in observations that provided specific insights into the structural mechanisms of its function. In this article, we describe a recent study by Ye et al. that reveals, using the human ATG3, how the membrane binding capability of the enzyme is tightly linked to its conjugation activity. We summarize the current knowledge on important mechanisms that involve protein-protein or protein-membrane interactions of Atg3 and that ultimately lead to efficient Atg8–PE conjugation.

Abbreviations: AH: amphipathic helix; FR: flexible region; HR: handle region; NMR: nuclear magnetic resonance

摘要

Atg3 蛋白在酵母和人之间具有高度同源性。Atg3 作为 E2 样酶发挥作用，促进 Atg8 家族蛋白与磷脂酰乙醇胺 (PE) 结合，这是一种在应激诱导的自噬过程中嵌入生长中的吞噬细胞膜的脂质分子。在过去十年中，Atg3 成为探索最多的自噬蛋白之一，其观察结果为其功能的结构机制提供了具体的见解。在本文中，我们描述了 Ye 等人最近的一项研究。这揭示了使用人类 ATG3 酶的膜结合能力如何与其结合活性密切相关。我们总结了目前关于涉及 Atg3 的蛋白质-蛋白质或蛋白质-膜相互作用的重要机制的知识，并最终导致有效的 Atg8-PE 缀合。

缩写： AH：两亲螺旋；FR：弹性区域；HR：处理区域；核磁共振：核磁共振