Institute for Pharmaceutical and Medicinal Chemistry, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
Centro de Bioinformática y Simulación Molecular (CBSM), Facultad de Ingeniería, Universidad de Talca, Talca, Chile.
Sci Rep. 2019 Jun 20;9(1):8869. doi: 10.1038/s41598-019-45189-w.
The structure, mechanism of action and copper stoichiometry of the transmembrane sensor domain of the plant ethylene receptor ETR1 and homologs have remained elusive, hampering the understanding on how the perception of the plant hormone ethylene is transformed into a downstream signal. We generated the first structural model of the transmembrane sensor domain of ETR1 by integrating ab initio structure prediction and coevolutionary information. To refine and independently validate the model, we determined protein-related copper stoichiometries on purified receptor preparations and explored the helix arrangement by tryptophan scanning mutagenesis. All-atom molecular dynamics simulations of the dimeric model reveal how ethylene can bind proximal to the copper ions in the receptor, illustrating the initial stages of the ethylene perception process.
植物乙烯受体 ETR1 及其同源物的跨膜传感器结构域的结构、作用机制和铜化学计量学一直难以捉摸，这阻碍了我们对植物激素乙烯的感知如何转化为下游信号的理解。我们通过整合从头计算结构预测和共进化信息，生成了 ETR1 跨膜传感器结构域的第一个结构模型。为了改进和独立验证该模型，我们在纯化的受体制剂上确定了与蛋白质相关的铜化学计量，并通过色氨酸扫描诱变探索了螺旋排列。二聚体模型的全原子分子动力学模拟说明了乙烯如何能结合到受体中铜离子的附近，阐明了乙烯感知过程的初始阶段。
