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首页> 外文期刊>Journal of Molecular Biology >Mechanisms for ligand binding to GluR0 ion channels: crystal structures of the glutamate and serine complexes and a closed apo state.
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Mechanisms for ligand binding to GluR0 ion channels: crystal structures of the glutamate and serine complexes and a closed apo state.

机译：配体与GluR0离子通道结合的机制：谷氨酸和丝氨酸复合物的晶体结构以及封闭的载脂蛋白状态。

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摘要

High-resolution structures of the ligand binding core of GluR0, a glutamate receptor ion channel from Synechocystis PCC 6803, have been solved by X-ray diffraction. The GluR0 structures reveal homology with bacterial periplasmic binding proteins and the rat GluR2 AMPA subtype neurotransmitter receptor. The ligand binding site is formed by a cleft between two globular alpha/beta domains. L-Glutamate binds in an extended conformation, similar to that observed for glutamine binding protein (GlnBP). However, the L-glutamate gamma-carboxyl group interacts exclusively with Asn51 in domain 1, different from the interactions of ligand with domain 2 residues observed for GluR2 and GlnBP. To address how neutral amino acids activate GluR0 gating we solved the structure of the binding site complex with L-serine. This revealed solvent molecules acting as surrogate ligand atoms, such that the serine OH group makes solvent-mediated hydrogen bonds with Asn51. The structure of a ligand-free, closed-cleft conformation revealed an extensive hydrogen bond network mediated by solvent molecules. Equilibrium centrifugation analysis revealed dimerization of the GluR0 ligand binding core with a dissociation constant of 0.8 microM. In the crystal, a symmetrical dimer involving residues in domain 1 occurs along a crystallographic 2-fold axis and suggests that tetrameric glutamate receptor ion channels are assembled from dimers of dimers. We propose that ligand-induced conformational changes cause the ion channel to open as a result of an increase in domain 2 separation relative to the dimer interface.
机译：X射线衍射已解决了GluR0的配体结合核心的高分辨率结构，GluR0是Synechocystis PCC 6803的谷氨酸受体离子通道。 GluR0结构揭示了与细菌周质结合蛋白和大鼠GluR2 AMPA亚型神经递质受体的同源性。配体结合位点由两个球形α/β域之间的裂缝形成。 L-谷氨酸以扩展构象结合，类似于谷氨酰​​胺结合蛋白（GlnBP）观察到的构象。但是，L-谷氨酸的γ-羧基仅与结构域1中的Asn51相互作用，这与针对GluR2和GlnBP观察到的配体与结构域2残基的相互作用不同。为了解决中性氨基酸如何激活GluR0门控的问题，我们解决了L-丝氨酸结合位点复合物的结构。这表明溶剂分子充当替代配体原子，因此丝氨酸OH基团与Asn51形成溶剂介导的氢键。无配体的闭合裂缝构象的结构揭示了由溶剂分子介导的广泛的氢键网络。平衡离心分析显示GluR0配体结合核心的二聚化具有0.8 microM的解离常数。在晶体中，对称的二聚体沿着晶体学的2倍轴出现，涉及域1中的残基，表明四聚谷氨酸受体离子通道由二聚体的二聚体组装而成。我们提出，由于相对于二聚体界面的结构域2分离的增加，配体诱导的构象变化导致离子通道打开。

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