日常生活中,，有些人幾乎一刻也離不開香煙,，這全都是人腦中的尼古丁受體“從中作祟”,。法國科學家日前成功繪制出了與尼古丁受體結(jié)構(gòu)相似的一種蛋白質(zhì)的三維圖像,，這將幫助人們更深入地認識尼古丁依賴,，從而找到控制煙癮的新方法,。
據(jù)法國媒體5日報道,，科學研究表明，煙草中的主要成分尼古丁被吸入體內(nèi)后與人腦中的特定受體結(jié)合,，促使大腦中的愉快中樞釋放多巴胺,，產(chǎn)生“犒賞效應”，這樣人們在吸煙時就會產(chǎn)生愉悅感,，從而對香煙產(chǎn)生嚴重依賴,。
科學家曾試圖獲得這種受體的三維圖像，但難題太多,，于是法國國家科研中心的一個研究小組另辟蹊徑,，找到了一種與尼古丁受體結(jié)構(gòu)十分相似的細菌蛋白質(zhì)，并繪制出了它的三維圖像,。
研究小組負責人皮埃爾－讓·戈林奇說,，這種蛋白質(zhì)與尼古丁受體雖然功能不盡相同，但從分子結(jié)構(gòu)的角度來看，它們之間具有很高的相似性,。
科學家認為,，他們的研究使人們對尼古丁受體的結(jié)構(gòu)有了更多了解，這是在研發(fā)戒煙新藥的道路上向前邁出的一大步,。
這一研究成果已發(fā)表在5日出版的英國《自然》雜志電子版上,。（生物谷Bioon.com）
生物谷推薦原始出處：
Nature advance online publication 5 November 2008 | doi:10.1038
X-ray structure of a pentameric ligand-gated ion channel in an apparently open conformation
Nicolas Bocquet1,5, Hugues Nury1,2,5, Marc Baaden4, Chantal Le Poupon1, Jean-Pierre Changeux3, Marc Delarue2 & Pierre-Jean Corringer1
1 Pasteur Institute, G5 Group of Channel-Receptor, CNRS URA 2182
2 Pasteur Institute, Unit of Structural Dynamics of Macromolecules, CNRS URA 2185
3 Pasteur Institute, CNRS URA 2182, F75015, Paris, France
4 Institut de Biologie Physico-Chimique, CNRS UPR 9080, 75005 Paris, France
5 These authors contributed equally to this work.
Pentameric ligand-gated ion channels from the Cys-loop family mediate fast chemo-electrical transduction1, 2, 3, but the mechanisms of ion permeation and gating of these membrane proteins remain elusive. Here we present the X-ray structure at 2.9 ? resolution of the bacterial Gloeobacter violaceus pentameric ligand-gated ion channel homologue4 (GLIC) at pH 4.6 in an apparently open conformation. This cationic channel is known to be permanently activated by protons5. The structure is arranged as a funnel-shaped transmembrane pore widely open on the outer side and lined by hydrophobic residues. On the inner side, a 5 ? constriction matches with rings of hydrophilic residues that are likely to contribute to the ionic selectivity6, 7, 8, 9. Structural comparison with ELIC, a bacterial homologue from Erwinia chrysanthemi solved in a presumed closed conformation10, shows a wider pore where the narrow hydrophobic constriction found in ELIC is removed. Comparative analysis of GLIC and ELIC reveals, in concert, a rotation of each extracellular -sandwich domain as a rigid body, interface rearrangements, and a reorganization of the transmembrane domain, involving a tilt of the M2 and M3 -helices away from the pore axis. These data are consistent with a model of pore opening based on both quaternary twist and tertiary deformation.
