Brake A J, Wagenbach M J, Julius D
Department of Pharmacology, University of California, San Francisco 94143-0450.
Nature. 1994 Oct 6;371(6497):519-23. doi: 10.1038/371519a0.
The adenosine-5'-triphosphate (ATP) molecule is an extracellular messenger in neural and non-neural tissues, where it activates several cell-surface-receptor subtypes, including G-protein-coupled receptors and ligand-gated ion channels. ATP-gated channels (termed P2x receptors) have been characterized on smooth muscle cells and autonomic and sensory neurons, where they mediate membrane depolarization and, in some cases, Ca2+ entry. P2x receptors are functionally heterogeneous, but resemble acetylcholine- and serotonin-gated channels with respect to ion selectivity and kinetic parameters of channel gating. We report here that despite such close functional similarities, the deduced sequence of a cloned P2x receptor predicts an unusual subunit structure resembling voltage-insensitive cation channels. Thus, the P2x receptor provides a striking example of convergent evolution, whereby proteins have been fashioned with similar functional properties from subunits having very different structural characteristics. There is sequence similarity between the ATP receptor and RP-2, a gene activated in thymocytes undergoing programmed cell death. RP-2 may encode a receptor for ATP or another metabolite released during apoptosis.
腺苷 - 5'-三磷酸（ATP）分子是神经组织和非神经组织中的一种细胞外信使，在这些组织中它可激活多种细胞表面受体亚型，包括G蛋白偶联受体和配体门控离子通道。ATP门控通道（称为P2x受体）已在平滑肌细胞、自主神经和感觉神经元中得到鉴定，在这些细胞中它们介导膜去极化，在某些情况下还介导Ca2+内流。P2x受体在功能上具有异质性，但在离子选择性和通道门控的动力学参数方面类似于乙酰胆碱和5-羟色胺门控通道。我们在此报告，尽管存在如此紧密的功能相似性，但克隆的P2x受体的推导序列预测其亚基结构不同寻常，类似于电压不敏感阳离子通道。因此，P2x受体提供了一个趋同进化的显著例子，即具有非常不同结构特征的亚基形成了具有相似功能特性的蛋白质。ATP受体与RP - 2之间存在序列相似性，RP - 2是在经历程序性细胞死亡的胸腺细胞中被激活的一个基因。RP - 2可能编码一种ATP受体或凋亡过程中释放的另一种代谢产物的受体。
