Molecular Determinants Elucidate the Selectivity in Abscisic Acid Receptor and HAB1 Protein Interactions
Molecular Determinants Elucidate the Selectivity in Abscisic Acid Receptor and HAB1 Protein Interactions
复制标题
分子决定因素阐明脱落酸受体和 HAB1 蛋白质相互作用的选择性。
DOI：
10.3389/fchem.2020.00425
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发表时间：
2020-06-04
影响因子：
5.5
通讯作者：
Yang, Guang-Fu
中科院分区：
文献类型：
--
作者：
Yang, Jing-Fang;Yin, Chun-Yan;Yang, Guang-Fu
脱落酸（阿坝）作为一种重要的植物激素，在调控植物的生命周期和适应环境胁迫中起着重要作用。阿坝的受体是阿坝受体的Pyrabactin抗性/Pyrabactin抗性样/调节组分（PYR/PYL/RCAR，为简单起见，PYL），其调节信号通路中的蛋白磷酸酶2Cs（PP 2Cs）。Pyrabactin作为一种重要的ABA模拟配体，对PYL的部分成员如PYR 1和PYL 1具有激活作用。由于Pyrabactin对PYL 2具有拮抗作用，因此它被用作发现部分阿坝受体的探针。此后，许多研究者一直试图找出PYL和PP 2Cs相互作用选择性调节的决定因素。然而，残基在Pyrabactin诱导的PYR 1/PYL 2和PP 2Cs相互作用的选择性调节中的作用仍然是不明确的。本研究通过序列比对、分子对接、分子动力学模拟、结合自由能计算等方法研究了吡拉菌素的选择性激活机制。比较了吡拉菌素与其激动剂在静电和疏水作用方面的差异。结果表明PYR 1/PYL 2的口袋和门的Leu 137/Val 114、Ser 85/Ser 89和Gly 86/Gly 90是选择性激活Pyrabactin的关键残基。同时，PP 2Cs与PYL类化合物的静电相互作用增强。这一机制为选择性激动剂和拮抗剂的设计提供了强有力的支持。
The abscisic acid (ABA), as a pivotal plant hormone, plays a key role in controlling the life cycle and adapting to the environmental stresses. The receptors of ABA are the Pyrabactin resistance/Pyrabactin resistance-like/regulatory component of ABA receptors (PYR/PYL/RCAR, PYLs for simplicity), which regulate the protein phosphatase 2Cs (PP2Cs) in the signal pathway. As an important ABA-mimicking ligand, Pyrabactin shows the activation function to parts of members of PYLs, such as PYR1 and PYL1. Due to the antagonism of Pyrabactin to PYL2, it was used as a probe to discover a part of ABA receptors. Since then, many researchers have been trying to find out the determinants of the selective regulation of PYLs and PP2Cs interaction. However, the roles of residues on the selective regulation of PYR1/PYL2 and PP2Cs interaction induced by Pyrabactin are still ambiguous. This research investigated the selective activation mechanism of Pyrabactin through the sequence alignment, molecular docking, molecular dynamics simulation, and binding free energy calculation. Furthermore, the electrostatic and hydrophobic interaction differences induced by Pyrabactin and agonists were compared. The results indicate that Leu137/Val114, Ser85/Ser89, and Gly86/Gly90 from the pocket and gate of PYR1/PYL2 are the vital residues for the selective activation of Pyrabactin. Meanwhile, the electrostatic interaction between PP2Cs and PYLs complexed with agonists was improved. This mechanism provides strong support for the design of selective agonists and antagonists.