日常生活中，有些人幾乎一刻也離不開(kāi)香煙,，這全都是人腦中的尼古丁受體“從中作祟”。法國(guó)科學(xué)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(rèn)識(shí)尼古丁依賴(lài),，從而找到控制煙癮的新方法,。
據(jù)法國(guó)媒體5日?qǐng)?bào)道，科學(xué)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(yīng)”,，這樣人們?cè)谖鼰煏r(shí)就會(huì)產(chǎn)生愉悅感,，從而對(duì)香煙產(chǎn)生嚴(yán)重依賴(lài)。
科學(xué)家曾試圖獲得這種受體的三維圖像,，但難題太多,，于是法國(guó)國(guó)家科研中心的一個(gè)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(xì)菌蛋白質(zhì),，并繪制出了它的三維圖像,。
研究小組負(fù)責(zé)人皮埃爾－讓·戈林奇說(shuō)，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(lái)看,，它們之間具有很高的相似性。
科學(xué)家認(rèn)為,，他們的研究使人們對(duì)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(guó)《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.
