Interrogating protein interaction networks through structural biology
Interrogating protein interaction networks through structural biology
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DOI：
10.1073/pnas.092147999
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发表时间：
2002-04-30
影响因子：
11.1
通讯作者：
Russell, RB
中科院分区：
文献类型：
--
作者：
Aloy, P;Russell, RB
蛋白质-蛋白质相互作用是大多数生物过程的核心。虽然最近的努力已经投入到方法，以确定相互作用的合作伙伴，有一个有限的重点是如何将这些相互作用与那些已知的三维（3D）结构。由于蛋白质相互作用的比较通常涉及考虑同源但不相同的蛋白质，因此关键问题是与相互作用对同源的蛋白质是否会以相同的方式相互作用，或者根本不相互作用。因此，我们描述了一种方法来测试已知的三维结构的复合物上假定的相互作用。给定一个3D复合物和相互作用蛋白质的同源物的比对，我们通过使用经验势评估复合物上任何可能的相互作用对的拟合。对于显示不同特异性的相互作用蛋白质家族的研究，该方法提供了用于优先实验的相互作用对的排名。我们评估的方法相互作用的蛋白质家族与多个复杂的结构。然后，我们考虑成纤维细胞生长因子/受体系统，并探讨已知结构的复合物和酵母蛋白质之间的相互作用的方法，如双杂交之间的交叉点。我们提供了几个相互作用的确认，除了建议它们如何发生的分子细节。
Protein-protein interactions are central to most biological processes. Although much recent effort has been put into methods to identify interacting partners, there has been a limited focus on how these interactions compare with those known from three-dimensional (3D) structures. Because comparison of protein interactions often involves considering homologous, but not identical, proteins, a key issue is whether proteins that are homologous to an interacting pair will interact in the same way, or interact at all. Accordingly, we describe a method to test putative interactions on complexes of known 3D structure. Given a 3D complex and alignments of homologues of the interacting proteins, we assess the fit of any possible interacting pair on the complex by using empirical potentials. For studies of interacting protein families that show different specificities, the method provides a ranking of interacting pairs useful for prioritizing experiments. We evaluate the method on interacting families of proteins with multiple complex structures. We then consider the fibroblast growth factor/receptor system and explore the intersection between complexes of known structure and interactions proposed between yeast proteins by methods such as two-hybrids. We provide confirmation for several interactions, in addition to suggesting molecular details of how they occur.