Ayyappan Vinay, Wat Ricky, Barber Calvin, Vivelo Christina A, Gauch Kathryn, Visanpattanasin Pat, Cook Garth, Sazeides Christos, Leung Anthony K L
Department of Biomedical Engineering, The G.W.C. Whiting School of Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA.
bioRxiv. 2020 Sep 25:2020.09.24.298851. doi: 10.1101/2020.09.24.298851.
ADP-ribosylation is a protein modification responsible for biological processes such as DNA repair, RNA regulation, cell cycle, and biomolecular condensate formation. Dysregulation of ADP-ribosylation is implicated in cancer, neurodegeneration, and viral infection. We developed ADPriboDB (adpribodb.leunglab.org) to facilitate studies in uncovering insights into the mechanisms and biological significance of ADP-ribosylation. ADPriboDB 2.0 serves as a one-stop repository comprising 48,346 entries and 9,097 ADP-ribosylated proteins, of which 6,708 were newly identified since the original database release. In this updated version, we provide information regarding the sites of ADP-ribosylation in 32,946 entries. The wealth of information allows us to interrogate existing databases or newly available data. For example, we found that ADP-ribosylated substrates are significantly associated with the recently identified human protein interaction networks associated with SARS-CoV-2, which encodes a conserved protein domain called macrodomain that binds and removes ADP-ribosylation. In addition, we create a new interactive tool to visualize the local context of ADP-ribosylation, such as structural and functional features as well as other post-translational modifications (e.g., phosphorylation, methylation and ubiquitination). This information provides opportunities to explore the biology of ADP-ribosylation and generate new hypotheses for experimental testing.
ADP核糖基化是一种蛋白质修饰，负责DNA修复、RNA调控、细胞周期和生物分子凝聚物形成等生物学过程。ADP核糖基化失调与癌症、神经退行性疾病和病毒感染有关。我们开发了ADPriboDB（adpribodb.leunglab.org），以促进对ADP核糖基化机制和生物学意义的研究。ADPriboDB 2.0是一个一站式知识库，包含48346个条目和9097个ADP核糖基化蛋白，其中自原始数据库发布以来新鉴定出6708个。在这个更新版本中，我们提供了32946个条目中ADP核糖基化位点的信息。丰富的信息使我们能够查询现有数据库或新获得的数据。例如，我们发现ADP核糖基化底物与最近鉴定的与严重急性呼吸综合征冠状病毒2（SARS-CoV-2）相关的人类蛋白质相互作用网络显著相关，该病毒编码一种名为宏结构域的保守蛋白质结构域，可结合并去除ADP核糖基化。此外，我们创建了一个新的交互式工具，以可视化ADP核糖基化的局部背景，如结构和功能特征以及其他翻译后修饰（如磷酸化、甲基化和泛素化）。这些信息为探索ADP核糖基化生物学和生成新的实验测试假设提供了机会。
