Post-translationally-modified structures in the autophagy machinery: an integrative perspective.
Post-translationally-modified structures in the autophagy machinery: an integrative perspective.
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DOI：
10.1111/febs.13356
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发表时间：
2015-09
期刊：
影响因子：
--
通讯作者：
Klionsky DJ
中科院分区：
文献类型：
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作者：
Popelka H;Klionsky DJ
自噬是发生在基础结构水平的自我清洁过程，在应激反应中被上调。巨噬（以下简称自噬）是最强大的自噬类型，其中货物（特异性或非特异性）被称为自噬体的双膜结构吞噬。这个过程需要严格调节，以维持正常的细胞稳态和防止功能障碍；因此，更全面地了解自噬调节机制对于理解整个途径至关重要。自噬相关蛋白（Atg）是进行自噬的主要成分。这些蛋白质中的许多从酵母到人类都是保守的。在研究自噬蛋白或其蛋白结构域的核磁共振或晶体结构的同时，也报道了许多关于蛋白功能域、蛋白-蛋白相互作用或自噬蛋白翻译后修饰的重大发现。在这项工作中，我们总结了迄今为止收集到的关于自噬机制的蛋白质的结构见解，这些蛋白质由翻译后修饰调节，特别是磷酸化，乙酰化，泛素化和/或sumo化。对于每种蛋白质，我们将报告的结果与相应氨基酸序列的有序/无序倾向信息联系起来。这种综合的方法对每个翻译后修饰的蛋白质进行了全面的概述，并揭示了进一步研究的领域。
Autophagy is self-cleaning process that occurs at a constitutive basal level, and is upregulated in response to stress. Macroautophagy (hereafter autophagy) is the most robust type of autophagy, where cargo (specific or nonspecific) is engulfed within a double-membrane structure termed an autophagosome. This process needs to be tightly regulated to maintain normal cellular homeostasis and prevent dysfunction; therefore, a fuller knowledge of the mechanisms of autophagy regulation is crucial for understanding the entire pathway. The autophagy-related (Atg) proteins are the primary components that carry out autophagy. Many of these proteins are conserved from yeast to human. A number of significant discoveries with regard to protein functional domains, protein-protein interactions, or posttranslational modifications of proteins involved in autophagy have been reported in parallel with, or followed by, solving the NMR or crystal structures of autophagy proteins or their protein domains. In this work, we summarize structural insights gathered to date on the proteins of the autophagy machinery that are modulated by a posttranslational modification, specifically phosphorylation, acetylation, ubiquitination, and/or SUMOylation. For each protein, we link the reported results with information on the propensity of the corresponding amino acid sequence toward order/disorder. This integrative approach yields a comprehensive overview for each posttranslationally modified protein, and also reveals areas for further investigation.