School of Natural and Environmental Sciences, Newcastle University, Newcastle upon Tyne NE1 7RU, UK.
Fontus Environmental, High Garth, Thirsk YO7 3PX, UK.
Int J Mol Sci. 2021 Feb 11;22(4):1806. doi: 10.3390/ijms22041806.
Phytosulfokine (PSK) is a phytohormone responsible for cell-to-cell communication in plants, playing a pivotal role in plant development and growth. The binding of PSK to its cognate receptor, PSKR1, is modulated by the formation of a binding site located between a leucine-rich repeat (LRR) domain of PSKR1 and the loop located in the receptor's island domain (ID). The atomic resolution structure of the extracellular PSKR1 bound to PSK has been reported, however, the intrinsic dynamics of PSK binding and the architecture of the PSKR1 binding site remain to be understood. In this work, we used atomistic molecular dynamics (MD) simulations and free energy calculations to elucidate how the PSKR1 island domain (ID) loop forms and binds PSK. Moreover, we report a novel "druggable" binding site which could be exploited for the targeted modulation of the PSKR1-PSK binding by small molecules. We expect that our results will open new ways to modulate the PSK signalling cascade via small molecules, which can result in new crop control and agricultural applications.
植物磺基丙氨酸（PSK）是一种在植物细胞间通讯中起作用的植物激素，在植物发育和生长中起着关键作用。PSK 与其同源受体 PSKR1 的结合受位于 PSKR1 的富含亮氨酸重复（LRR）结构域和受体岛域（ID）中的环之间的结合位点的形成所调节。已经报道了与 PSK 结合的细胞外 PSKR1 的原子分辨率结构，但是 PSK 结合的固有动力学和 PSKR1 结合位点的结构仍有待理解。在这项工作中，我们使用原子分子动力学（MD）模拟和自由能计算来阐明 PSKR1 岛域（ID）环如何形成并结合 PSK。此外，我们报告了一种新的“可成药”结合位点，可通过小分子对 PSKR1-PSK 结合进行靶向调节。我们期望我们的结果将为通过小分子调节 PSK 信号级联提供新的途径，从而为新的作物控制和农业应用提供可能。
