Activation and desensitization of ionotropic glutamate receptors by selectively triggering pre-existing motions.
Activation and desensitization of ionotropic glutamate receptors by selectively triggering pre-existing motions.
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DOI：
10.1016/j.neulet.2018.02.050
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发表时间：
2019-05-01
影响因子：
2.5
通讯作者：
Bahar I
中科院分区：
文献类型：
--
作者：
Krieger J;Lee JY;Greger IH;Bahar I
内在运动揭示离子型谷氨酸受体结构域之间的耦合。域之间的变构通信选择性地利用预先存在的运动。全球动力学促进激活，变构信号和脱敏。弹性网络模型有效地阐明了iGluRs的预先存在的动力学。离子型谷氨酸受体（iGluRs）是配体门控的离子通道，其是突触传递和可塑性的关键参与者。它们由四个亚基组成，每个亚基包含四个功能结构域，其四级堆积和集体结构动力学是其分子功能机制的重要决定因素。随着对该家族不同成员的结构研究的激增，包括激活的开放通道的结构，这些中央信号机的作用机制现在正在阐明。我们回顾了目前的计算研究的家庭，AMPA和NMDA受体的两个主要成员，重点是分子模拟和弹性网络模型分析，提供了深入了解细胞外和跨膜结构域的耦合运动。我们描述了新出现的激活机制，变构信号和脱敏，主要是一个选择性触发预先存在的软运动，推导出的计算模型和分析，利用结构数据完整的AMPA和NMDA受体在不同的状态。
Intrinsic motions reveal couplings between ionotropic glutamate receptor domains. Allosteric communication between domains selectively exploits pre-existing motions. Global dynamics facilitates activation, allosteric signaling and desensitization. Elastic network models efficiently elucidate the pre-existing dynamics of iGluRs. Ionotropic glutamate receptors (iGluRs) are ligand-gated ion channels that are key players in synaptic transmission and plasticity. They are composed of four subunits, each containing four functional domains, the quaternary packing and collective structural dynamics of which are important determinants of their molecular mechanism of function. With the explosion of structural studies on different members of the family, including the structures of activated open channels, the mechanisms of action of these central signaling machines are now being elucidated. We review the current state of computational studies on two major members of the family, AMPA and NMDA receptors, with focus on molecular simulations and elastic network model analyses that have provided insights into the coupled movements of extracellular and transmembrane domains. We describe the newly emerging mechanisms of activation, allosteric signaling and desensitization, as mainly a selective triggering of pre-existing soft motions, as deduced from computational models and analyses that leverage structural data on intact AMPA and NMDA receptors in different states.
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AMPA受体GLUA2在休息，预开口和脱敏状态中的结构和动力学。
影响因子：
64.5
作者：
Dürr KL;Chen L;Stein RA;De Zorzi R;Folea IM;Walz T;Mchaourab HS;Gouaux E
通讯作者：
Gouaux E
影响因子：
8.8
作者：
Cais O;Herguedas B;Krol K;Cull-Candy SG;Farrant M;Greger IH
通讯作者：
Greger IH
影响因子：
16.6
作者：
Dong H;Zhou HX
通讯作者：
Zhou HX
DOI：
10.1016/j.str.2015.07.002
发表时间：
2015-09-01
期刊：
Structure (London, England : 1993)
影响因子：
--
作者：
Dutta A;Krieger J;Lee JY;Garcia-Nafria J;Greger IH;Bahar I
通讯作者：
Bahar I
影响因子：
4.8
作者：
Dolino, Drew M.;Cooper, David;Jayaraman, Vasanthi
通讯作者：
Jayaraman, Vasanthi