Co-evolution of proteins with their interaction partners
Co-evolution of proteins with their interaction partners
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DOI：
10.1006/jmbi.2000.3732
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发表时间：
2000-06-02
影响因子：
5.6
通讯作者：
Cohen, FE
中科院分区：
文献类型：
--
作者：
Goh, CS;Bogan, AA;Cohen, FE
细胞信号传导途径中蛋白质的发散进化需要配体及其受体共同进化，当新配体激活新受体时创建新途径。然而，仅从序列中很难收集有关配体-受体系统中结合特异性进化的信息。我们使用磷酸甘油酸激酶（PGK）（一种在其两个结构域之间形成活性位点的酶）来开发测量相互作用蛋白质的共同进化的标准。 PGK 的 N 端和 C 端结构域在其界面处形成活性位点并共价连接。因此，它们必须共同进化以保持酶的功能。通过根据 PGK 两个域中每个域的多个序列比对构建两个系统发育树，我们计算了两个树的相关系数，该系数量化了两个域的协同进化。 PGK 两个结构域树的相关系数为 0.79，它确定了蛋白质结构域与其结合伴侣共同进化的上限。使用趋化因子作为模型，该分析扩展到配体及其受体。我们发现趋化因子配体和受体树距离之间的相关性为 0.57。蛋白质配体的趋化因子家族及其 G 蛋白偶联受体共同进化，因此趋化因子配体的每个亚组都具有匹配的趋化因子受体亚组。配体及其受体的匹配亚家族创建了一个框架，在该框架内可以更容易地确定孤儿趋化因子受体的配体。该方法可应用于多种配体和受体系统。(C) 2000 学术出版社。
The divergent evolution of proteins in cellular signaling pathways requires ligands and their receptors to co-evolve, creating new pathways when a new receptor is activated by a new Ligand. However, information about the evolution of binding specificity in Ligand-receptor systems is difficult to glean from sequences alone. We have used phosphoglycerate kinase (PGK), an enzyme that forms its active site between its two domains, to develop a standard for measuring the co-evolution of interacting proteins. The N-terminal and C-terminal domains of PGK form the active site at their interface and are covalently linked. Therefore, they must have co-evolved to preserve enzyme function. By building two phylogenetic trees from multiple sequence alignments of each of the two domains of PGK, we have calculated a correlation coefficient for the two trees that quantifies the coevolution of the two domains. The correlation coefficient for the trees of the two domains of PGK is 0.79, which establishes an upper bound for the co-evolution of a protein domain with its binding partner. The analysis is extended to ligands and their receptors, using the chemokines as a model. We show that the correlation between the chemokine ligand and receptor trees' distances is 0.57. The chemokine family of protein ligands and their G-protein coupled receptors have coevolved so that each subgroup of chemokine Ligands has a matching subgroup of chemokine receptors. The matching subfamilies of Ligands and their receptors create a framework within which the ligands of orphan chemokine receptors can be more easily determined. This approach can be applied to a variety of Ligand and receptor systems.(C) 2000 Academic Press.