Giorgetti Alejandro, Nair Anil V, Codega Paolo, Torre Vincent, Carloni Paolo
Istituto Nazionale per la Fisica della Materia and International School for Advanced Studies, Via Beirut 4, 34014 Trieste, Italy.
FEBS Lett. 2005 Mar 28;579(9):1968-72. doi: 10.1016/j.febslet.2005.01.086.
Cyclic nucleotide-gated (CNG) ion channels, underlying sensory transduction in vertebrate photoreceptors and olfactory sensory neurons, require cyclic nucleotides to open. Here, we present structural models of the tetrameric CNG channel pore from bovine rod in both open and closed states, as obtained by combining homology modeling-based techniques, experimentally derived spatial constraints and structural patterns present in the PDB database. Gating is initiated by an anticlockwise rotation of the N-terminal region of the C-linker, which is then, transmitted through the S6 transmembrane helices to the P-helix, and in turn from this to the pore lumen, which opens up from 2 to 5A thus allowing for ion permeation. The approach, here presented, is expected to provide a general methodology for model ion channels and their gating when structural templates are available and an extensive electrophysiological analysis has been performed.
环核苷酸门控(CNG)离子通道是脊椎动物光感受器和嗅觉感觉神经元中感觉转导的基础,需要环核苷酸来开启。在此,我们展示了牛视杆细胞四聚体CNG通道孔在开放和关闭状态下的结构模型,这些模型是通过结合基于同源建模的技术、实验得出的空间限制以及PDB数据库中存在的结构模式获得的。门控由C连接子N端区域的逆时针旋转启动,然后通过S6跨膜螺旋传递到P螺旋,再从P螺旋传递到孔腔,孔腔从2埃扩大到5埃,从而允许离子通透。当有结构模板且已进行广泛的电生理分析时,本文提出的方法有望为模拟离子通道及其门控提供一种通用方法。