Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1QW, UK.
Biochem Soc Trans. 2009 Dec;37(Pt 6):1343-6. doi: 10.1042/BST0371343.
The Cys-loop family of ligand-gated ion channels contains both vertebrate and invertebrate members that are activated by GABA (gamma-aminobutyric acid). Many of the residues that are critical for ligand binding have been identified in vertebrate GABA(A) and GABA(C) receptors, and specific interactions between GABA and some of these residues have been determined. In the present paper, I show how a cation-pi interaction for one of the binding site residues has allowed the production of models of GABA docked into the binding site, and these orientations are supported by mutagenesis and functional data. Surprisingly, however, the residue that forms the cation-pi interaction is not conserved, suggesting that GABA occupies subtly different locations even in such closely related receptors.
Cys 环家族的配体门控离子通道包含脊椎动物和无脊椎动物成员，它们被 GABA（γ-氨基丁酸）激活。在脊椎动物 GABA(A) 和 GABA(C) 受体中已经确定了许多对配体结合至关重要的残基，并且已经确定了 GABA 与其中一些残基之间的特定相互作用。在本文中，我展示了一个结合位点残基的阳离子-π 相互作用如何允许 GABA 对接入结合位点的模型的产生，并且这些取向得到了突变和功能数据的支持。然而，令人惊讶的是，形成阳离子-π 相互作用的残基并不保守，这表明即使在如此密切相关的受体中，GABA 占据的位置也略有不同。
