Cooperative Dynamics of Intact AMPA and NMDA Glutamate Receptors: Similarities and Subfamily-Specific Differences.
Cooperative Dynamics of Intact AMPA and NMDA Glutamate Receptors: Similarities and Subfamily-Specific Differences.
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DOI：
10.1016/j.str.2015.07.002
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发表时间：
2015-09-01
期刊：
影响因子：
--
通讯作者：
Bahar I
中科院分区：
文献类型：
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作者：
Dutta A;Krieger J;Lee JY;Garcia-Nafria J;Greger IH;Bahar I
离子型谷氨酸受体（iGluRs）是介导兴奋性神经传递的四聚体离子通道。AMPA和NMDA受体的最新结构允许第一次对整个受体动力学进行比较分析。尽管其两个结构域的胞外区的包装有很大的差异，两个iGluRs共享相似的动力学，阐明了弹性网络模型。可接近任一结构的运动使构象相互转换成为可能，例如AMPAR向更紧密堆积的NMDAR构象压缩，这与变构调节有关。枢转运动耦合到跨膜离子通道的协同旋转是突出的远端N-末端结构域的松散包装的AMPAR的二聚体之间。这些运动的发生和功能的相关性进行了验证，旨在探测计算预测的距离变化的交联实验。再加上热点残基作为介质的别构通信的识别，我们的数据提供了一个一瞥iGluRs的动态谱。
Ionotropic glutamate receptors (iGluRs) are tetrameric ion channels that mediate excitatory neurotransmission. Recent structures of AMPA and NMDA receptors permit a comparative analysis of whole-receptor dynamics for the first time. Despite substantial differences in the packing of their two-domain extracellular region, the two iGluRs share similar dynamics, elucidated by elastic network models. Motions accessible to either structure enable conformational interconversion, such as compression of the AMPAR towards the more tightly packed NMDAR conformation, which has been linked to allosteric regulation. Pivoting motions coupled to concerted rotations of the transmembrane ion channel are prominent between dimers of distal N-terminal domains in the loosely-packed AMPAR. The occurrence and functional relevance of these motions is verified by cross-linking experiments designed to probe the computationally predicted distance changes. Together with the identification of hot-spot residues acting as mediators of allosteric communication, our data provide a glimpse into the dynamic spectrum of iGluRs.