《生命科学》 2015, 27(2): 203-207

P2X4受体的结构功能关系研究进展

李　彬^1，2，3，卢向阳^1，2，于　烨^1，2，3*，田　云^1，2*

(¹ 湖南农业大学生物科学技术学院，长沙 410128；² 湖南省农业生物工程研究所，长沙 410128；³ 上海交通大学医学院，上海 200025)

摘　要：摘　要：嘌呤能受体P2X4 是三磷酸腺苷(ATP)- 门控的阳离子通道，对生物体内多种重要生命活动起一定的调节作用。二次跨膜的三聚体通道P2X4 受体的三维空间组成是由胞外结构域、跨膜域及胞内N-、C- 端组成。ATP 的三磷酸基团能被位于亚基界面的ATP 结合口袋的带正电氨基酸特异性识别，嘌呤环则被疏水氨基酸和部分氨基酸的主链氧所识别。P2X4 受体激活后，胞外阳离子更多是通过侧窗路径进入细胞内。就P2X4 受体的空间结构、配体的识别、离子通透途径及门控机制作一综述。

Research progress on structure and activity of P2X4 receptors

LI Bin^1，2，3， LU Xiang-Yang^1，2， YU Ye^1，2，3*， TIAN Yun^1，2*

(¹ College of Bioscience and Biotechnology， Hunan Agricultural University， Changsha 410128， China; ² Hunan Agricultural Bioengineering Research Institute， Changsha 410128， China; ³ Shanghai Jiao Tong University School of Medicine， Shanghai 200025， China)

Abstract: Abstract: P2X4 receptors are ATP-gated non-selective trimetric cation channels involved in various physiological processes. Each subunit is comprised of intracellular amino and carboxyl termini linked via two transmembrane (TM)-spanning helices (TM1 and TM2) to a large extracellular (EC) ligand-binding domain. A large ATP-binding pocket is located at the subunit interface of P2X4 receptors， which is occupied by a conspicuous cluster of basic residues (K70， K72， R298 and K316， zebrafish P2X4 numbering， similarly hereinafter) to recognize triphosphate moiety of ATP. The adenine ring makes contacts with L191， K70， K72， I232 and T186 via hydrophobic contacts or hydrogen bonds. Conformational changes both in EC and TM domain induced by ATP binding have been proposed. Two potential pathways (central and lateral) exist through which ions traverse the EC domain of P2X4 receptors to enter or exit the TM pore. Here， we summarize the progress in recent findings on the three dimensional architecture， ligand recognition， ion permeation pathway， and gating mechanism of P2X4 receptors.