Plant J|香港中文大学生科院利用拟南芥互作组数据系统预测自噬相关蛋白
自噬是一个自我降解的过程，通过清除受损的细胞质成分和循环营养物质来维持细胞的动态平衡是至关重要的。这种进化保守的蛋白水解过程受自噬相关蛋白(ATG)的调控。
对植物自噬蛋白质组的不完全理解和蛋白质组对自噬途径的广泛理解的重要性促使我们预测拟南芥中的ATG蛋白和调控因子。
本研究我们开发了一种系统水平的算法来识别自噬相关模块(ARM)，该算法基于蛋白质亚细胞定位、蛋白质-蛋白质相互作用和已知的ATG蛋白，从而生成了拟南芥中自噬模块的详细图景。
我们发现，在拟南芥的衰老过程中，每条臂中新发现的基因倾向于上调和共表达。我们还通过模块聚类和功能分析证明了高尔基体ARM(ARM13)在自噬过程中的作用。
为了验证电子分析，我们选择了ARM13中在功能上与核心ATG蛋白相似的ATG候选序列进行实验验证。
有趣的是，从ARM分析中鉴定出的两个以前未鉴定的蛋白质，AGD1和Sec14，显示了与植物细胞中的自噬蛋白复合物的真正联系，这为细胞内途径和自噬之间的相关关系提供了证据。
因此，该计算框架有助于在高等真核生物中鉴定和鉴定植物特异的自噬相关蛋白和新的自噬蛋白/调控因子。
Autophagy is a self‐degradative process that is crucial for maintaining cellular homeostasis by removing damaged cytoplasmic components and recycling nutrients. Such an evolutionary conserved proteolysis process is regulated by the autophagy‐related (Atg) proteins. The incomplete understanding of plant autophagy proteome and the importance of a proteome‐wide understanding of the autophagy pathway prompted us to predict Atg proteins and regulators in Arabidopsis. Here, we developed a systems‐level algorithm to identify autophagy‐related modules (ARMs) based on protein subcellular localization, protein‐protein interactions and known Atg proteins.This generates a detailed landscape of the autophagic modules in Arabidopsis. We found that the newly identified genes in each ARM tend to be up‐regulated and co‐expressed during the senescence stage of Arabidopsis. We also demonstratedthat the Golgi apparatus ARM, ARM13, functions in the autophagy process by module clustering and functional analysis. To verify the in silico analysis, the Atg candidates in ARM13 that are functionally similar to the core Atg proteins were selected for experimental validation. Interestingly, two of the previously uncharacterized proteins identified from the ARM analysis, AGD1 and Sec14, exhibited bona fide association with the autophagy protein complexinplant cells, which provides evidence for a cross‐talk between intracellular pathways and autophagy. Thus, the computational framework has facilitated the identification and characterization of plant specific autophagy‐related proteins and novel autophagy proteins/regulators in higher eukaryotes.
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