The Dynamic Multisite Interactions between Two Intrinsically Disordered Proteins.
The Dynamic Multisite Interactions between Two Intrinsically Disordered Proteins.
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DOI：
10.1002/anie.201701883
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发表时间：
2017-06
影响因子：
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通讯作者：
Shaowen Wu;Dongdong Wang;Jin Liu;Yitao Feng;J. Weng;Yu Li;Xin Gao;Jianwei Liu;Wenning Wang
中科院分区：
文献类型：
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作者：
Shaowen Wu;Dongdong Wang;Jin Liu;Yitao Feng;J. Weng;Yu Li;Xin Gao;Jianwei Liu;Wenning Wang
蛋白质相互作用涉及内在无序蛋白质（IDP）包括各种结合模式，从充分表征的折叠后结合到动态模糊复合物。迄今为止，大多数研究关注IDP与结构蛋白的结合，而对两个IDP之间的相互作用知之甚少。在这项研究中，NMR，smFRET和分子动力学（MD）模拟相结合，以表征两个IDP，蛋白质4.1G的C-末端结构域（CTD）和核有丝分裂器（NuMA）蛋白之间的相互作用。结果表明，CTD和NuMA形成了一个模糊的复杂的剩余结构的障碍。通过分子动力学和诱变研究确定了两种蛋白质上的多个结合位点。这项研究提供了一个原子的情况下，两个IDP轴承多个结合位点相互作用的动态平衡。这里采用的综合办法可广泛适用于调查国内流离失所者及其动态互动。
Protein interactions involving intrinsically disordered proteins (IDPs) comprise a variety of binding modes, from the well-characterized folding upon binding to dynamic fuzzy complexes. To date, most studies concern the binding of an IDP to a structured protein, while the interaction between two IDPs is poorly understood. In this study, NMR, smFRET, and molecular dynamics (MD) simulation are combined to characterize the interaction between two IDPs, the C-terminal domain (CTD) of protein 4.1G and the nuclear mitotic apparatus (NuMA) protein. It is revealed that CTD and NuMA form a fuzzy complex with remaining structural disorder. Multiple binding sites on both proteins were identified by molecular dynamics and mutagenesis studies. This study provides an atomic scenario in which two IDPs bearing multiple binding sites interact with each other in dynamic equilibrium. The combined approach employed here could be widely applicable for investigating IDPs and their dynamic interactions.