The oligonucleotide/oligosaccharide-binding (OB)-fold domain proteins are considered as genome guardians, whose functions are extending beyond genomic stability. The broad functional diversity of the OB-fold proteins is attributed to their protein-DNA, protein-RNA, and protein-protein interactions (PPI). To understand the connectivity of the human OB-fold proteins, we report here a systems-level approach. Specifically, we mapped all human OB-fold PPI networks and evaluated topological features such as network robustness and network hub, among others. We found that the OB-fold network comprised of 227 nodes forming 5523 interactions, and has a scale-free topology having UBA52, ATR, and TP53 as leading hub proteins that control efficient communication within the network. Furthermore, four different clusters and subclusters have been identified, which are implicated in diverse cellular processes, including DNA replication, repair, maintenance of genomic stability, RNA processing, spermatogenesis, complement system, and telomere maintenance. The importance of these clusters is further strengthened by knockout studies, which showed a significant decrease in topological properties. In summary, this study provides new insights on the role of OB-fold protein as genome guardians in regard to the underlying mechanism of signaling pathways, the roles of key regulators, and thus, offers new prospects as potential targets for diagnostics and therapeutics purposes.

中文翻译：

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基因组守护者的系统视图：映射寡核苷酸/寡糖结合折叠蛋白基础的信号通路。

寡核苷酸/寡糖结合 (OB) 折叠域蛋白被认为是基因组守护者，其功能超出了基因组稳定性。OB 折叠蛋白的广泛功能多样性归因于它们的蛋白质-DNA、蛋白质-RNA 和蛋白质-蛋白质相互作用 (PPI)。为了了解人类 OB 折叠蛋白的连通性，我们在此报告了一种系统级方法。具体来说，我们绘制了所有人类 OB-fold PPI 网络，并评估了网络稳健性和网络集线器等拓扑特征。我们发现 OB 折叠网络由 227 个节点组成，形成 5523 个交互，并且具有无标度拓扑，其中 UBA52、ATR 和 TP53 作为控制网络内有效通信的主要枢纽蛋白。此外，已经确定了四个不同的集群和子集群，它们涉及多种细胞过程，包括 DNA 复制、修复、基因组稳定性的维持、RNA 加工、精子发生、补体系统和端粒维持。敲除研究进一步加强了这些簇的重要性，结果表明拓扑特性显着下降。总之，这项研究为 OB 折叠蛋白作为基因组守护者的作用提供了新的见解，涉及信号通路的潜在机制、关键调节剂的作用，因此为诊断和治疗目的的潜在目标提供了新的前景。敲除研究进一步加强了这些簇的重要性，结果表明拓扑特性显着下降。总之，这项研究为 OB 折叠蛋白作为基因组守护者的作用提供了新的见解，涉及信号通路的潜在机制、关键调节剂的作用，因此为诊断和治疗目的的潜在目标提供了新的前景。敲除研究进一步加强了这些簇的重要性，结果表明拓扑特性显着下降。总之，这项研究为 OB 折叠蛋白作为基因组守护者的作用提供了新的见解，涉及信号通路的潜在机制、关键调节剂的作用，因此为诊断和治疗目的的潜在目标提供了新的前景。