PULSED ESR STUDY OF CONFORMATIONAL CHANGES OF A GLUTAMATE BINDING DOMAIN

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 谷氨酸受体离子通道（GluRs）是中枢神经系统突触的重要组成部分，它将化学信号转化为电脉冲。 化学信使谷氨酸与细胞外配体结合结构域（GluR S1 S2）的结合诱导GluR的构象转变，从而打开通道，允许离子电流刺激神经。 通过激动剂或拮抗剂结合，GluR S1 S2在通道激活和脱敏中起关键作用。 虽然脱辅基状态的晶体结构给出了一个开放的配体结合裂缝的静态图片，但初步的计算研究表明脱辅基结构的变化程度更大。 初始脉冲ESR实验的目的是提供有关载脂蛋白和配体结合态的叶分离距离分布的信息。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Glutamate receptor ion channels (GluRs), which convert a chemical signal into an electrical impulse, are essential components of central nervous system synapses. Binding of the chemical messenger, glutamate, to the extracellular ligand-binding domain (GluR S1S2) induces a conformational transition in the GluRs thereby opening the channel to allow ionic current to stimulate the nerve. Through agonist or antagonist binding the GluR S1S2 plays a key role in channel activation and desensitization. While crystal structures of the apo-state give a static picture of an open ligand-binding cleft, preliminary computational studies have suggested a larger degree of variation in the apo-structure. Initial pulsed ESR experiments are aimed at providing information on the distribution of lobe separation distances in apo and ligand bound states.