Pang Erli, Tan Tao, Lin Kui
Beijing Normal University, Beijing, China.
Mol Biosyst. 2012 Mar;8(3):766-71. doi: 10.1039/c1mb05364g. Epub 2011 Dec 14.
Domain-domain interactions are a critical type of the mechanisms mediating protein-protein interactions (PPIs). For a given protein domain, its ability to combine with distinct domains is usually referred to as promiscuity or versatility. Interestingly, a previous study has reported that a domain's promiscuity may reflect its ability to interact with other domains in human proteins. In this work, promiscuous domains were first identified from the yeast genome. Then, we sought to determine what roles promiscuous domains might play in the PPI network. Mapping the promiscuous domains onto the proteins in this network revealed that, consistent with the previous knowledge, the hub proteins were significantly enriched with promiscuous domains. We also found that the set of hub proteins were not the same set as those proteins with promiscuous domains, although there was some overlap. Analysis of the topological properties of this yeast PPI network showed that the characteristic path length of the network increased significantly after deleting proteins with promiscuous domains. This indicated that communication between two proteins was longer and the network stability decreased. These observations suggested that, as the hub proteins, proteins with promiscuous domains might play a role in maintaining network stability. In addition, functional analysis revealed that proteins with promiscuous domains mainly participated in the "Folding, Sorting, and Degradation" and "Replication and Repair" biological pathways, and that they significantly execute key molecular functions, such as "nucleoside-triphosphatase activity (GO:0017111)."
结构域-结构域相互作用是介导蛋白质-蛋白质相互作用（PPI）的关键机制类型。对于给定的蛋白质结构域，其与不同结构域结合的能力通常被称为混杂性或多功能性。有趣的是，先前的一项研究报告称，一个结构域的混杂性可能反映其与人类蛋白质中其他结构域相互作用的能力。在这项工作中，首先从酵母基因组中鉴定出混杂结构域。然后，我们试图确定混杂结构域在PPI网络中可能发挥的作用。将混杂结构域映射到该网络中的蛋白质上发现，与先前的认识一致，枢纽蛋白显著富集有混杂结构域。我们还发现，枢纽蛋白集与具有混杂结构域的蛋白集并不相同，尽管存在一些重叠。对该酵母PPI网络的拓扑特性分析表明，删除具有混杂结构域的蛋白质后，网络的特征路径长度显著增加。这表明两个蛋白质之间的通信变长，网络稳定性下降。这些观察结果表明，作为枢纽蛋白，具有混杂结构域的蛋白质可能在维持网络稳定性方面发挥作用。此外，功能分析表明，具有混杂结构域的蛋白质主要参与“折叠、分选和降解”以及“复制和修复”生物途径，并且它们显著执行关键分子功能，如“核苷三磷酸酶活性（GO:0017111）”。
