Crystal structure of the extracellular domain of nAChR alpha1 bound to alpha-bungarotoxin at 1.94 A resolution.
Crystal structure of the extracellular domain of nAChR alpha1 bound to alpha-bungarotoxin at 1.94 A resolution.
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发表时间：
2007
影响因子：
25
通讯作者：
C. Dellisanti;Yun Yao;J. Stroud;Zuo-Zhong Wang;Lin Chen
中科院分区：
文献类型：
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作者：
C. Dellisanti;Yun Yao;J. Stroud;Zuo-Zhong Wang;Lin Chen
我们确定了小鼠烟碱乙酰胆碱受体（nAChR）α 1亚基结合α-银环蛇毒素在1.94 A分辨率的细胞外结构域的晶体结构。该结构是nAChR亚基胞外结构域的第一个原子分辨率视图，揭示了受体特异性特征，如主要免疫原性区域（MIR），签名Cys环和N-连接的碳水化合物链。毒素通过广泛的蛋白质-蛋白质和蛋白质-糖相互作用与受体结合。令我们惊讶的是，该结构显示了一个有序的水分子和两个亲水性残基，位于α 1亚基的核心深处。这两个亲水性核心残基在nAChRs中高度保守，但对应于非通道同源物乙酰胆碱结合蛋白中的疏水性残基。我们进行了定点突变和电生理学分析，以评估糖基化和亲水性核心残基的功能作用。我们的结构和功能研究显示了nAChR的基本特征，并为门控机制提供了新的见解。
We determined the crystal structure of the extracellular domain of the mouse nicotinic acetylcholine receptor (nAChR) alpha1 subunit bound to alpha-bungarotoxin at 1.94 A resolution. This structure is the first atomic-resolution view of a nAChR subunit extracellular domain, revealing receptor-specific features such as the main immunogenic region (MIR), the signature Cys-loop and the N-linked carbohydrate chain. The toxin binds to the receptor through extensive protein-protein and protein-sugar interactions. To our surprise, the structure showed a well-ordered water molecule and two hydrophilic residues deep in the core of the alpha1 subunit. The two hydrophilic core residues are highly conserved in nAChRs, but correspond to hydrophobic residues in the nonchannel homolog acetylcholine-binding proteins. We carried out site-directed mutagenesis and electrophysiology analyses to assess the functional role of the glycosylation and the hydrophilic core residues. Our structural and functional studies show essential features of the nAChR and provide new insights into the gating mechanism.