Scaffolding functions of arrestin-2 revealed by crystal structure and mutagenesis
Scaffolding functions of arrestin-2 revealed by crystal structure and mutagenesis
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DOI：
10.1021/bi015905j
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发表时间：
2002-03-12
期刊：
影响因子：
2.9
通讯作者：
Benovic, JL
中科院分区：
文献类型：
--
作者：
Milano, SK;Pace, HC;Benovic, JL
Arrestin与活化的磷酸化G蛋白偶联受体（GPCR）结合是调节光和光依赖性信号传导的关键步骤。非视觉arrestins，如arrestin-2，与多种蛋白质相互作用，以传播和终止信号事件。结合X射线晶体学、分子建模、诱变和结合分析，我们揭示了arrestin-2的结构特征，这些特征可能使其能够同时结合磷酸化受体、SH 3结构域、磷酸肌醇和β-适应素。因此，全长arrestin-2的结构为参与GPCR信号转导的多个不同分子的组装提供了独特定向的支架。
Arrestin binding to activated, phosphorylated G protein-coupled receptors (GPCRs) represents a critical step in regulation of light- and hormone-dependent signaling. Nonvisual arrestins, such as arrestin-2, interact with multiple proteins for the purpose of propagating and terminating signaling events. Using a combination of X-ray crystallography, molecular modeling, mutagenesis, and binding analysis, we reveal structural features of arrestin-2 that may enable simultaneous binding to phosphorylated receptor, SH3 domains, phosphoinositides, and beta-adaptin. The structure of full-length arrestin-2 thus provides a uniquely oriented scaffold for assembly of multiple, diverse molecules involved in GPCR signal transduction.