生物谷綜合：當(dāng)尼古丁結(jié)合到神經(jīng)細(xì)胞時(shí),，細(xì)胞如何發(fā)送信號使吸煙者產(chǎn)生好的感覺？答案或許是糖,。來自Southern California大學(xué)的科學(xué)家最近發(fā)現(xiàn)糖能打開細(xì)胞膜上的大門,，使尼古丁進(jìn)入，這一結(jié)果在線發(fā)表在近日的Nature Neuroscience上,。
結(jié)構(gòu)生物學(xué)家Raymond Stevens認(rèn)為這是“結(jié)構(gòu)生物學(xué)和神經(jīng)細(xì)胞信號領(lǐng)域里程碑似的成就,。”除了煙癮患者外，癲癇,、精神分裂和抑郁癥患者也能從這一研究中獲得好處,。
研究首次提供了老鼠的尼古丁乙酰膽堿受體（nAChR）部分詳細(xì)結(jié)構(gòu)，nAChR屬于一類很重要的分子,，它們充當(dāng)離子通道蛋白,，使信號在兩個(gè)神經(jīng)元間傳遞。而研究結(jié)果顯示糖分子在這種蛋白中起到了重要作用,。
分子和計(jì)算生物學(xué)副教授Lin Chen認(rèn)為,，目前的很多理論沒有考慮糖的作用，因此它們可能并不完整,。關(guān)于信號如何從細(xì)胞外傳入細(xì)胞內(nèi)的爭論已經(jīng)持續(xù)了很久。某些科學(xué)家認(rèn)為當(dāng)化學(xué)物質(zhì)（例如尼古?。┙Y(jié)合到細(xì)胞表面的離子通道蛋白時(shí),，蛋白會(huì)通過“構(gòu)象波”將信號傳到細(xì)胞膜。但這種波的分子學(xué)機(jī)制并不清楚,。
而Chen的小組提出了糖類的一種簡單作用機(jī)制,。同時(shí)科學(xué)家還發(fā)現(xiàn)在受體的核心部分存在一個(gè)水分子，這很重要因?yàn)橥ǔ５鞍踪|(zhì)會(huì)充滿了疏水物質(zhì)以保持其結(jié)構(gòu),。水分子使得受體可以改變自身結(jié)構(gòu)以實(shí)現(xiàn)平衡,。nAChR的類似分子幾乎完全是疏水的，這證明了存在于內(nèi)部的水分子起到了功能上的作用,。 （援引教育部科技發(fā)展中心）
原文鏈接：http://www.physorg.com/news104332097.html
原始出處:
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 [email protected] or [email protected]
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.
