Nature Neurosci：糖分子有助于尼古丁影响神经细胞
生物谷综合：当尼古丁结合到神经细胞时，细胞如何发送信号使吸烟者产生好的感觉？答案或许是糖。来自Southern California大学的科学家最近发现糖能打开细胞膜上的大门，使尼古丁进入，这一结果在线发表在近日的Nature Neuroscience上。
结构生物学家Raymond Stevens认为这是“结构生物学和神经细胞信号领域里程碑似的成就。”除了烟瘾患者外，癫痫、精神分裂和抑郁症患者也能从这一研究中获得好处。
研究首次提供了老鼠的尼古丁乙酰胆碱受体（nAChR）部分详细结构，nAChR属于一类很重要的分子，它们充当离子通道蛋白，使信号在两个神经元间传递。而研究结果显示糖分子在这种蛋白中起到了重要作用。
分子和计算生物学副教授Lin Chen认为，目前的很多理论没有考虑糖的作用，因此它们可能并不完整。关于信号如何从细胞外传入细胞内的争论已经持续了很久。某些科学家认为当化学物质（例如尼古丁）结合到细胞表面的离子通道蛋白时，蛋白会通过“构象波”将信号传到细胞膜。但这种波的分子学机制并不清楚。
而Chen的小组提出了糖类的一种简单作用机制。同时科学家还发现在受体的核心部分存在一个水分子，这很重要因为通常蛋白质会充满了疏水物质以保持其结构。水分子使得受体可以改变自身结构以实现平衡。nAChR的类似分子几乎完全是疏水的，这证明了存在于内部的水分子起到了功能上的作用。 （援引教育部科技发展中心）
原文链接：http://www.physorg.com/news104332097.html
原始出处:
Nature Neuroscience
Published online: 22 July 2007; | doi:10.1038/nn1942
Crystal structure of the extracellular domain of nAChR 
1 bound to -bungarotoxin at 1.94 Å resolution
Cosma D Dellisanti1, 2, 3, Yun Yao4, James C Stroud5, Zuo-Zhong Wang4 & Lin Chen1, 2, 3
1 Molecular and Computation Biology, University of Southern California, 1050 Childs Way, RIH201, Los Angeles, California 90089-2910, USA. 2 Department of Chemistry, University of Southern California, 1050 Childs Way, RIH201, Los Angeles, California 90089-2910, USA. 3 Norris Cancer Center, University of Southern California, 1050 Childs Way, RIH201, Los Angeles, California 90089-2910, USA. 4 Zilkha Neurogenetic Institute, Department of Cell and Neurobiology, Keck School of Medicine, University of Southern California, 1501 San Pablo St., ZNI101, Los Angeles, California 90033, USA. 5 University of California Los Angeles, Department of Energy, Institute for Genomics and Proteomics, 611 Young Dr. East, Los Angeles, California 90095-1570, USA. Correspondence should be addressed to Zuo-Zhong WangLin Chen linchen@usc.edu or zzwang@usc.edu We determined the crystal structure of the extracellular domain of the mouse nicotinic acetylcholine receptor (nAChR) 
1 subunit bound to -bungarotoxin at 1.94 Å 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 1 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.
美国科学家发现“烟瘾基因”
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