Structure of the S1S2 glutamate binding domain of GLuR3.
Structure of the S1S2 glutamate binding domain of GLuR3.
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DOI：
10.1002/prot.22274
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发表时间：
2009-05-15
影响因子：
2.9
通讯作者：
Oswald, Robert E.
中科院分区：
文献类型：
--
作者：
Ahmed, Ahmed H.;Wang, Qi;Sondermann, Holger;Oswald, Robert E.
谷氨酸受体是脊椎动物中枢神经系统中最常见的兴奋性神经递质受体。确定不同亚型结合部位之间的结构差异对于我们理解神经元回路和开发亚型特异性药物至关重要。X射线结晶学测定谷氨酸和AMPA结合的GluR3(FliP)AMPA受体亚单位的结合域(S1S2)和与谷氨酸结合的GluR2(Flop)亚单位的结构分别为1.9、2.1和1.55 a.总体而言，GluR3(FliP)S1S2的结构与GluR2(Flop)S1S2非常相似(主干RMSD分别为0.30±0.05和0.26±0.01(谷氨酸结合和AMPA结合)。翻转和翻转异构体之间的差异是微妙的，主要是因为二聚体界面上的一个氢键和相关的水分子。比较各种激动剂和部分激动剂的结合亲和力表明，GluR2和GluR3的S1S2结构域仅显示出微小的亲和力差异，与完整受体不同(除了一个配体Cl-Hibo，它对GluR2和GluR3的亲和力相差10倍)。
Glutamate receptors are the most prevalent excitatory neurotransmitter receptors in the vertebrate central nervous system. Determining the structural differences between the binding sites of different subtypes is crucial to our understanding of neuronal circuits and to the development of subtype specific drugs. The structures of the binding domain (S1S2) of the GluR3 (flip) AMPA receptor subunit bound to glutamate and AMPA and the GluR2 (flop) subunit bound to glutamate were determined by X-ray crystallography to 1.9, 2.1, and 1.55 Å, respectively. Overall, the structure of GluR3 (flip) S1S2 is very similar to GluR2 (flop) S1S2 (backbone RMSD of 0.30 ± 0.05 for glutamate-bound and 0.26 ± 0.01 for AMPA-bound). The differences in the flip and flop isoforms are subtle and largely arise from one hydrogen bond across the dimer interface and associated water molecules. Comparison of the binding affinity for various agonists and partial agonists suggest that the S1S2 domains of GluR2 and GluR3 show only small differences in affinity, unlike what is found for the intact receptors (with the exception of one ligand, Cl-HIBO, which has a ten-fold difference in affinity for GluR2 vs GluR3).
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DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
2.9
作者：
McFeeters, RL;Oswald, RE
通讯作者：
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影响因子：
5.3
作者：
Banke, TG;Greenwood, JR;Pickering, DS
通讯作者：
Pickering, DS
影响因子：
2.9
作者：
Hayward, S;Lee, RA
通讯作者：
Lee, RA
影响因子：
4.8
作者：
Ahmed, H. Ahmed;Loh, Adrienne P.;Oswald, Robert E.
通讯作者：
Oswald, Robert E.