Armstrong N, Gouaux E
Department of Biochemistry and Molecular Biophysics, Columbia University, New York, New York 10032, USA.
Neuron. 2000 Oct;28(1):165-81. doi: 10.1016/s0896-6273(00)00094-5.
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 approximately equal 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 effectors modulate receptor activity.
已确定谷氨酸受体2（GluR2）配体结合核心（S1S2）在无配体状态下以及存在拮抗剂DNQX、部分激动剂海人酸和完全激动剂AMPA及谷氨酸时的晶体结构。S1S2配体结合核心的结构域在无配体状态下是扩展的，在配体结合时会收缩，结构域分离程度按无配体＞DNQX＞海人酸＞谷氨酸（约等于AMPA）的顺序降低。这些结果表明，激动剂诱导的结构域闭合控制着跨膜通道，受体激活程度取决于结构域闭合程度。AMPA和谷氨酸还会促使配体结合位点中的一个反式肽键发生180度翻转。配体结合核心的晶体堆积表明了完整受体中亚基-亚基接触的模式以及变构效应剂调节受体活性的机制。
