Molecular dynamics simulations of the conformational changes of the glutamate receptor ligand‐binding core in the presence of glutamate and kainate
Molecular dynamics simulations of the conformational changes of the glutamate receptor ligand‐binding core in the presence of glutamate and kainate
复制标题
谷氨酸和红藻氨酸存在下谷氨酸受体配体结合核心构象变化的分子动力学模拟
DOI：
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发表时间：
2001
期刊：
影响因子：
--
通讯作者：
F. Gago
中科院分区：
文献类型：
--
作者：
J. Mendieta;G. Ramı́rez;F. Gago
兴奋性突触传递是由嗜离子性谷氨酸受体（iGluRs）通过诱导跨膜离子通道的瞬时开放介导的。iGluRs的胞外配体结合核心的三维结构与细菌周围质结合蛋白（PBPs）的整体特征相同。在这两个蛋白家族中，配体结合位点排列在两个由裂缝分隔的结构域中，并由两个肽段连接。PBPs经历与配体结合相关的两个结构域的典型铰链运动，导致构象从开放到封闭形式的变化。共同的结构表明，在特异性激动剂结合诱导的iGluRs的配体结合核心中存在类似的关闭机制。从实验确定的S1S2 GluR2结构的盐酸盐结合闭合形式开始，我们通过分子动力学模拟研究了在谷氨酸和盐酸盐存在和不存在的情况下配体结合核的开放运动。我们的研究结果表明，区域间铰链运动的打开/关闭与跨膜片段插入区域的构象变化有关。这些变化是由激动剂与必需的Glu 209残基相互作用引起的。讨论了激动剂结合与通道门控耦合的可能机制。蛋白质2001;44:460 - 469。©2001 Wiley‐Liss, Inc。
Excitatory synaptic transmission is mediated by ionotropic glutamate receptors (iGluRs) through the induced transient opening of transmembrane ion channels. The three‐dimensional structure of the extracellular ligand‐binding core of iGluRs shares the overall features of bacterial periplasmic binding proteins (PBPs). In both families of proteins, the ligand‐binding site is arranged in two domains separated by a cleft and connected by two peptide stretches. PBPs undergo a typical hinge motion of the two domains associated with ligand binding that leads to a conformational change from an open to a closed form. The common architecture suggests a similar closing mechanism in the ligand‐binding core of iGluRs induced by the binding of specific agonists. Starting from the experimentally determined kainate‐bound closed form of the S1S2 GluR2 construct, we have studied by means of molecular dynamics simulations the opening motion of the ligand‐binding core in the presence and in the absence of both glutamate and kainate. Our results suggest that the opening/closing interdomain hinge motions are coupled to conformational changes in the insertion region of the transmembrane segments. These changes are triggered by the interaction of the agonists with the essential Glu 209 residue. A plausible mechanism for the coupling of agonist binding to channel gating is discussed. Proteins 2001;44:460–469. © 2001 Wiley‐Liss, Inc.
谷氨酸受体通道 M2 上的单个色氨酸赋予二价阳离子高渗透性。
影响因子：
3.4
作者：
Ferrer-Montiel,AV;Sun,W;Montal,M
通讯作者：
Montal,M
影响因子：
56.9
作者：
Rosenmund, C;Stern-Bach, Y;Stevens, CF
通讯作者：
Stevens, CF
N-糖基化揭示了两个红藻氨酸受体亚基的跨膜拓扑。
DOI：
10.1073/pnas.91.15.7154
发表时间：
1994
影响因子：
11.1
作者：
Wo,ZG;Oswald,RE
通讯作者：
Oswald,RE