A genome-wide Ras-effector interaction network
A genome-wide Ras-effector interaction network
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DOI：
10.1016/j.jmb.2007.05.015
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发表时间：
2007-07-27
影响因子：
5.6
通讯作者：
Serrano, Luis
中科院分区：
文献类型：
--
作者：
Kiel, Christina;Foglierini, Mathilde;Serrano, Luis
在这里，使用结构信息和蛋白质设计工具，我们绘制了20个Ras亚家族蛋白与50个假定的Ras结合结构域之间的相互作用网络。为了验证这个网络，我们克隆了六个特征不佳的Ras结合结构域（RBD）和两个Ras蛋白（RERG，DiRas 1）。这些，连同先前描述的RBD结构域，Ras和Rap蛋白已经在70个下拉实验中进行了分析。将我们的相互作用网络与这些和以前的下拉实验（总共150个案例）进行比较，显示出区分粘合剂和非粘合剂的非常高的准确性（类似于0.80）。整合了生物信息学信息，以区分那些更可能与体内相关的体外相互作用。我们提出了几个新的Ras家族成员和效应结构域之间的相互作用，是相关的了解这些蛋白质的生理作用。更广泛地说，我们的研究结果表明，蛋白质家族成员之间的（结构域-结构域）相互作用特异性可以准确地预测使用结构信息。(c)2007爱思唯尔有限公司保留所有权利。
Here using structural information and protein design tools we have drawn the network of interactions between 20 Ras subfamily proteins with 50 putative Ras binding domains. To validate this network we have cloned six poorly characterized Ras binding domains (RBD) and two Ras proteins (RERG, DiRas1). These, together with previously described RBD domains, Ras and Rap proteins have been analyzed in 70 pull-down experiments. Comparing our interaction network with these and previous pull-down experiments (total of 150 cases) shows a very high accuracy for distinguishing between binders and non-binders (similar to 0.80). Bioinformatics information was integrated to distinguish those in vitro interactions that are more likely to be relevant in vivo. We proposed several new interactions between Ras family members and effector domains that are of relevance in understanding the physiological role of these proteins. More broadly our results demonstrate that (domain-domain) interaction specificities between members of protein families can be accurately predicted using structural information. (c) 2007 Elsevier Ltd. All rights reserved.