首页> 外文期刊>Journal of Biomolecular Structure and Dynamics >Identification of the Structural Features that Mediate Binding Specificity in the Recognition of STAT Proteins by Dual-Specificity Phosphatases.
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Identification of the Structural Features that Mediate Binding Specificity in the Recognition of STAT Proteins by Dual-Specificity Phosphatases.

机译:通过双特异性磷酸酶识别介导统计蛋白质结合特异性的结构特征。

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摘要

Inactivation of signal transducers and activators of transcription (STAT) proteins is regulated by dual-specificity phosphatases (DSPs) with high substrate specificity. Although experiments have provided useful information about the phosphatase activity and the specificity for STATs, there is up-to-date no data at a molecular level to explain the specific recognition of STAT substrates by this subfamily of phosphatases. Here, a combined approach of molecular modeling, docking and molecular dynamics simulations was used to address the binding between DSPs and their STAT substrates. We identified a binding interface at the protein tyrosine phosphatase (PTP) domain of the DSP VHR that interacts with the SH2-domain of STAT5. This finding is consistent with previous mutational data and supports a "two-step" mechanism for the dephosphorylation event. Application of the same approach suggests the presence of a similar interface between the viral DSP VH1 and STAT1. Furthermore, the interaction network at this interface provides an explanation for the specificity of the DSP-STAT recognition.
机译:通过具有高底物特异性的双特异性磷酸酶(DSP)调节信号传感器和转录激活剂的失活,具有高底物特异性。尽管实验已经提供有关磷酸酶活性的有用信息和统计数据的特异性,但是在分子水平上最新的没有数据,以解释该亚家族的磷酸酶的统计底物的具体识别。这里,使用分子建模,对接和分子动力学模拟的组合方法来解决DSP与其统计衬底之间的结合。我们鉴定了DSP VHR的蛋白质酪氨酸磷酸酶(PTP)结构域的结合界面,其与STAT5的SH2结构域相互作用。此发现与先前的突变数据一致,支持用于去磷酸化事件的“两步”机制。相同方法的应用表明病毒DSP VH1和Stat1之间存在类似的界面。此外,该接口处的交互网络提供了对DSP-STAT识别的特异性的说明。

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