Mechanisms for activation and antagonism of an AMPA-Sensitive glutamate receptor: Crystal structures of the GluR2 ligand binding core
Mechanisms for activation and antagonism of an AMPA-Sensitive glutamate receptor: Crystal structures of the GluR2 ligand binding core
复制标题
DOI：
10.1016/s0896-6273(00)00094-5
复制
发表时间：
2000-10-01
期刊：
影响因子：
16.2
通讯作者：
Gouaux, E
中科院分区：
文献类型：
--
作者：
Armstrong, N;Gouaux, E
GluR 2配体结合核心（S1 S2）的晶体结构已在载脂蛋白状态下和在拮抗剂DNQX、部分激动剂红藻氨酸盐和完全激动剂AMPA和谷氨酸盐的存在下测定。S1 S2配体结合核心的结构域在apo状态下扩展，并且在配体结合时收缩，结构域分离的程度以apo > DNQX >红藻氨酸盐>与AMPA一致的谷氨酸盐的顺序降低。这些结果表明，激动剂诱导的域关闭门跨膜通道和受体激活的程度取决于域关闭的程度。AMPA和谷氨酸还促进配体结合位点中的反式肽键的180度翻转。配体结合核心的晶体包装表明在完整受体中亚基-亚基接触的模式和变构效应物调节受体活性的机制。
Crystal structures of the GluR2 ligand binding core (S1S2) have been determined in the apo state and in the presence of the antagonist DNQX, the partial agonist kainate, and the full agonists AMPA and glutamate. The domains of the S1S2 ligand binding core are expanded in the apo state and contract upon ligand binding with the extent of domain separation decreasing in the order of apo > DNQX > kainate > glutamate congruent to AMPA. These results suggest that agonist-induced domain closure gates the transmembrane channel and the extent of receptor activation depends upon the degree of domain closure. AMPA and glutamate also promote a 180 degrees flip of a trans peptide bond in the ligand binding site. The crystal packing of the ligand binding cores suggests modes for subunit-subunit contact in the intact receptor and mechanisms by which allosteric effecters modulate receptor activity.