Evidence for dynamically organized modularity in the yeast protein-protein interaction network
Evidence for dynamically organized modularity in the yeast protein-protein interaction network
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DOI：
10.1038/nature02555
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发表时间：
2004-07-01
期刊：
影响因子：
64.8
通讯作者：
Vidal, M
中科院分区：
文献类型：
--
作者：
Han, JDJ;Bertin, N;Vidal, M
在明显无标度的蛋白质-蛋白质相互作用网络或“相互作用组”网络中（1,2），大多数蛋白质与很少的伙伴相互作用，而一小部分但重要的蛋白质，即“枢纽”，与许多伙伴相互作用。生物和非生物无标度网络都特别抵抗随机节点移除，但对集线器的靶向移除极为敏感(1)。相互作用组网络的潜在无标度拓扑结构与遗传稳健性之间似乎存在联系（3,4），因为编码枢纽的酵母基因（5,6）的敲除比非枢纽的敲除更有可能导致死亡(1)。在这里，我们研究如何枢纽可能有助于鲁棒性和其他细胞性质的蛋白质蛋白质相互作用在时间和空间动态调节。我们发现了两种类型的中心：“聚会”中心，他们同时与大多数伴侣互动；“约会”中心，他们在不同的时间或地点绑定不同的伴侣。网络连接的计算机研究和体内描述的遗传相互作用都支持有组织的模块化模型，其中数据中心组织蛋白质组，将生物过程（或模块）相互连接(7)，而聚会中心在模块内部起作用。
In apparently scale-free protein-protein interaction networks, or 'interactome' networks(1,2), most proteins interact with few partners, whereas a small but significant proportion of proteins, the 'hubs', interact with many partners. Both biological and nonbiological scale-free networks are particularly resistant to random node removal but are extremely sensitive to the targeted removal of hubs(1). A link between the potential scale-free topology of interactome networks and genetic robustness(3,4) seems to exist, because knockouts of yeast genes(5,6) encoding hubs are approximately threefold more likely to confer lethality than those of non-hubs(1). Here we investigate how hubs might contribute to robustness and other cellular properties for protein protein interactions dynamically regulated both in time and in space. We uncovered two types of hub: 'party' hubs, which interact with most of their partners simultaneously, and 'date' hubs, which bind their different partners at different times or locations. Both in silico studies of network connectivity and genetic interactions described in vivo support a model of organized modularity in which date hubs organize the proteome, connecting biological processes-or modules(7)-to each other, whereas party hubs function inside modules.