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首页> 外文期刊>Acta crystallographica. Section D, Biological crystallography. >Genuine open form of the pentameric ligand-gated ion channel GLIC
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Genuine open form of the pentameric ligand-gated ion channel GLIC

机译:真正的开放形式pentameric ligand-gated离子通道GLIC

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摘要

Pentameric ligand-gated ion channels (pLGICs) mediate fast chemical neurotransmission of nerve signalling in the central and peripheral nervous systems. GLIC is a bacterial homologue of eukaryotic pLGIC, the X-ray structure of which has been determined in three different conformations. GLIC is thus widely used as a model to study the activation and the allosteric transition of this family of receptors. The recently solved high-resolution structure of GLIC (2.4 angstrom resolution) in the active state revealed two bound acetate molecules in the extracellular domain (ECD). Here, it is shown that these two acetates exactly overlap with known sites of pharmacological importance in pLGICs, and their potential influence on the structure of the open state is studied in detail. Firstly, experimental evidence is presented for the correct assignment of these acetate molecules by using the anomalous dispersion signal of bromoacetate. Secondly, the crystal structure of GLIC in the absence of acetate was solved and it is shown that acetate binding induces local conformational changes that occur in strategic sites of the ECD. It is expected that this acetate-free structure will be useful in future computational studies of the gating transition in GLIC and other pLGICs.
机译:Pentameric ligand-gated离子通道(pLGICs)调解的快速化学神经传递神经在中央和周围神经信号系统。真核pLGIC, x射线结构已经决定在三个不同构象。模型研究激活和变构过渡这个家族的受体。最近解决了高分辨率GLIC结构在活动状态(2.4埃分辨率)显示两个绑定醋酸分子细胞外的域(ECD)。这两个醋酸纤维素完全重叠已知药理重要的网站pLGICs及其潜在的影响详细研究了结构的开放状态。首先,给出了实验证据正确的分配这些醋酸分子通过使用反常色散的信号bromoacetate。醋酸GLIC没有解决它表明醋酸绑定引发当地吗构象变化发生在战略儿童早期开发的网站。acetate-free结构在将来会有用的计算控制过渡的研究GLIC和其他pLGICs。

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