Activity of Minimal NMDA Receptors

这个项目将描述缺乏N-末端和C-末端的NMDA受体的功能特性 结构域，这里指的是最小受体。这些蛋白质构成了NMDA的核心机制 受体，包括连接到离子渗透孔的细胞外激动剂结合结构域(ABD) 由跨膜(TMD)结构域形成。在父项目中，我们成功地使用了结构 这个最小受体的模型，用分子动力学来预测NMDA受体的开放轨迹 模拟。然而，目前尚不清楚最小受体是否具有功能，因此它们是否具有功能 为进一步的结构-功能研究提供了一个合适的模型，该模型基于 我们的模拟。在这个应用中，我们建议研究最小NMDA受体的假设 显示谷氨酸介导的离子亲和性。我们的初步结果表明，最小受体对 通过产生与野生型受体在动力学上不同的兴奋电流来产生谷氨酸。通过划定 微小NMDA受体激活机制与天然受体的异同 接受者，这个项目的结果将提供正确解释结果所必需的信息 分子动力学模拟。

This project will characterize the functional properties of NMDA receptors that lack N-terminal and C-terminal domains, herein referred to as minimal receptors. These proteins consist of the core machinery of NMDA receptors and include the extracellular agonist-binding domain (ABD) connected to the ion-permeable pore formed by the transmembrane (TMD) domain. In the parent project, we were successful in using a structural model of this minimal receptor to envision the opening trajectory of NMDA receptors, using molecular dynamics simulations. However, it is unknown whether the minimal receptors are functional and therefore whether they represent a suitable model for further structure-function investigations, based on the hypotheses generated by our simulations. In this application, we propose to investigate the hypothesis that minimal NMDA receptors display glutamate-mediated ionotropy. Our preliminary results demonstrate that minimal receptors respond to glutamate by producing excitatory currents that differ in kinetics from wild-type receptors. By delineating commonalities and differences between the activation mechanism of minimal NMDA receptors and native receptors, results from this project will provide information necessary for the correct interpretation of results from molecular dynamics simulations.