日常生活中，有些人几乎一刻也离不开香烟，这全都是人脑中的尼古丁受体“从中作祟”。法国科学家日前成功绘制出了与尼古丁受体结构相似的一种蛋白质的三维图像，这将帮助人们更深入地认识尼古丁依赖，从而找到控制烟瘾的新方法。
据法国媒体5日报道，科学研究表明，烟草中的主要成分尼古丁被吸入体内后与人脑中的特定受体结合，促使大脑中的愉快中枢释放多巴胺，产生“犒赏效应”，这样人们在吸烟时就会产生愉悦感，从而对香烟产生严重依赖。
科学家曾试图获得这种受体的三维图像，但难题太多，于是法国国家科研中心的一个研究小组另辟蹊径，找到了一种与尼古丁受体结构十分相似的细菌蛋白质，并绘制出了它的三维图像。
研究小组负责人皮埃尔－让·戈林奇说，这种蛋白质与尼古丁受体虽然功能不尽相同，但从分子结构的角度来看，它们之间具有很高的相似性。
科学家认为，他们的研究使人们对尼古丁受体的结构有了更多了解，这是在研发戒烟新药的道路上向前迈出的一大步。
这一研究成果已发表在5日出版的英国《自然》杂志电子版上。（生物谷Bioon.com）
生物谷推荐原始出处：
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.
