6月7日，Structure杂志在线报道了Atg12-Atg5偶联的结构基础。为深入理解自噬这一重要的生命现象，提供了新的重要信息。
Atg12-Atg5偶联，由一种泛素样偶联系统形成，对自噬复合体的形成具有关键作用。但Atg12-Atg5偶联形成的分子机制一直不明。
该研究解析了一种耐热酵母，克鲁维酵母菌属（Km）的Atg10和Atg5同源体。Km Atg10包含一个带有特征性附件的E2核心折叠，包括两个β链。而Km Atg5带有两个泛素样结构域和一个螺旋结构域。
核磁共振实验、突变分析以及交联实验显示Km Atg10通过其特征性β链，直接识别Km Atg5，特别是其C-末端的泛素样结构域。动力学分析提示，Km Atg10的Tyr56和Asn114可将Km Atg5Lys145的侧链置于与Atg12发生偶联反应的最佳取向。这样的结构特征使Atg10在无需特异性E3酶的条件下，介导Atg12-Atg5偶联的形成。（生物谷bioon.com)
doi:10.1016/j.cell.2011.10.017
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Structural Insights into Atg10-Mediated Formation of the Autophagy-Essential Atg12-Atg5 Conjugate
Masaya Yamaguchi, Nobuo N. Noda, Hayashi Yamamoto, Takayuki Shima, Hiroyuki Kumeta, Yoshihiro Kobashigawa, Rinji Akada
The Atg12-Atg5 conjugate, which is formed by an ubiquitin-like conjugation system, is essential to autophagosome formation, a central event in autophagy. Despite its importance, the molecular mechanism of the Atg12-Atg5 conjugate formation has not been elucidated. Here, we report the solution and crystal structures of Atg10 and Atg5 homologs from Kluyveromyces marxianus (Km), a thermotolerant yeast. KmAtg10 comprises an E2-core fold with characteristic accessories, including two β strands, whereas KmAtg5 has two ubiquitin-like domains and a helical domain. The nuclear magnetic resonance experiments, mutational analyses, and crosslinking experiments showed that KmAtg10 directly recognizes KmAtg5, especially its C-terminal ubiquitin-like domain, by its characteristic two β strands. Kinetic analysis suggests that Tyr56 and Asn114 of KmAtg10 may place the side chain of KmAtg5 Lys145 into the optimal orientation for its conjugation reaction with Atg12. These structural features enable Atg10 to mediate the formation of the Atg12-Atg5 conjugate without a specific E3 enzyme.
