Niss Kristoffer, Gomez-Casado Cristina, Hjaltelin Jessica X, Joeris Thorsten, Agace William W, Belling Kirstine G, Brunak Søren
Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark.
Immunology Section, Lund University, BMC D14, 221-84 Lund, Sweden; Institute of Applied Molecular Medicine, Faculty of Medicine, San Pablo CEU University, 28925 Madrid, Spain.
Cell Rep. 2020 Jun 16;31(11):107763. doi: 10.1016/j.celrep.2020.107763.
The network topology of a protein interactome is shaped by the function of each protein, making it a resource of functional knowledge in tissues and in single cells. Today, this resource is underused, as complete network topology characterization has proved difficult for large protein interactomes. We apply a matrix visualization and decoding approach to a physical protein interactome of a dendritic cell, thereby characterizing its topology with no prior assumptions of structure. We discover 294 proteins, each forming topological motifs called "bow-ties" that tie together the majority of observed protein complexes. The central proteins of these bow-ties have unique network properties, display multifunctional capabilities, are enriched for essential proteins, and are widely expressed in other cells and tissues. Collectively, the bow-tie motifs are a pervasive and previously unnoted topological trend in cellular interactomes. As such, these results provide fundamental knowledge on how intracellular protein connectivity is organized and operates.
蛋白质相互作用组的网络拓扑结构由每个蛋白质的功能塑造而成，使其成为组织和单细胞中功能知识的一个来源。如今，这一资源未得到充分利用，因为对于大型蛋白质相互作用组而言，完整的网络拓扑特征描述已被证明颇具难度。我们将一种矩阵可视化和解码方法应用于树突状细胞的物理蛋白质相互作用组，从而在不预先假设结构的情况下对其拓扑结构进行表征。我们发现了294种蛋白质，每种蛋白质都形成了被称为“领结”的拓扑基序，这些基序将大多数观察到的蛋白质复合物连接在一起。这些领结结构的核心蛋白质具有独特的网络特性，展现出多功能能力，富含必需蛋白质，并且在其他细胞和组织中广泛表达。总体而言，领结基序是细胞相互作用组中一种普遍存在且此前未被注意到的拓扑趋势。因此，这些结果提供了关于细胞内蛋白质连接如何组织和运作的基础知识。
