Jacomin Anne-Claire, Samavedam Siva, Promponas Vasilis, Nezis Ioannis P
a School of Life Sciences, University of Warwick , Coventry , UK.
b Bioinformatics Research Laboratory, Department of Biological Sciences, University of Cyprus , Nicosia , Cyprus.
Autophagy. 2016 Oct 2;12(10):1945-1953. doi: 10.1080/15548627.2016.1207016. Epub 2016 Aug 2.
Atg8-family proteins are the best-studied proteins of the core autophagic machinery. They are essential for the elongation and closure of the phagophore into a proper autophagosome. Moreover, Atg8-family proteins are associated with the phagophore from the initiation of the autophagic process to, or just prior to, the fusion between autophagosomes with lysosomes. In addition to their implication in autophagosome biogenesis, they are crucial for selective autophagy through their ability to interact with selective autophagy receptor proteins necessary for the specific targeting of substrates for autophagic degradation. In the past few years it has been revealed that Atg8-interacting proteins include not only receptors but also components of the core autophagic machinery, proteins associated with vesicles and their transport, and specific proteins that are selectively degraded by autophagy. Atg8-interacting proteins contain a short linear LC3-interacting region/LC3 recognition sequence/Atg8-interacting motif (LIR/LRS/AIM) motif which is responsible for their interaction with Atg8-family proteins. These proteins are referred to as LIR-containing proteins (LIRCPs). So far, many experimental efforts have been carried out to identify new LIRCPs, leading to the characterization of some of them in the past 10 years. Given the need for the identification of LIRCPs in various organisms, we developed the iLIR database ( https://ilir.warwick.ac.uk ) as a freely available web resource, listing all the putative canonical LIRCPs identified in silico in the proteomes of 8 model organisms using the iLIR server, combined with a Gene Ontology (GO) term analysis. Additionally, a curated text-mining analysis of the literature permitted us to identify novel putative LICRPs in mammals that have not previously been associated with autophagy.
Atg8家族蛋白是核心自噬机制中研究最为深入的蛋白。它们对于吞噬泡延伸并闭合形成合适的自噬体至关重要。此外,从自噬过程起始直至自噬体与溶酶体融合之前或刚好在此之前,Atg8家族蛋白都与吞噬泡相关联。除了参与自噬体生物发生外,它们通过与自噬降解底物特异性靶向所需的选择性自噬受体蛋白相互作用,对选择性自噬也至关重要。在过去几年中,已发现与Atg8相互作用的蛋白不仅包括受体,还包括核心自噬机制的组分、与囊泡及其运输相关的蛋白,以及被自噬选择性降解的特定蛋白。与Atg8相互作用的蛋白含有一个短线性的LC3相互作用区域/LC3识别序列/Atg8相互作用基序(LIR/LRS/AIM)基序,该基序负责它们与Atg8家族蛋白的相互作用。这些蛋白被称为含LIR的蛋白(LIRCPs)。到目前为止,已经开展了许多实验工作来鉴定新的LIRCPs,在过去10年中对其中一些进行了表征。鉴于需要在各种生物体中鉴定LIRCPs,我们开发了iLIR数据库(https://ilir.warwick.ac.uk)作为一个免费的网络资源,列出了使用iLIR服务器在8种模式生物的蛋白质组中通过计算机模拟鉴定出的所有推定的典型LIRCPs,并结合了基因本体(GO)术语分析。此外,通过对文献进行精心的文本挖掘分析,我们得以在哺乳动物中鉴定出以前未与自噬相关联的新型推定LICRPs。