NEW STRUCTURAL MOTIF FOR LIGAND-GATED ION CHANNELS DEFINED BY AN IONOTROPIC ATP RECEPTOR
NEW STRUCTURAL MOTIF FOR LIGAND-GATED ION CHANNELS DEFINED BY AN IONOTROPIC ATP RECEPTOR
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DOI：
10.1038/371519a0
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发表时间：
1994-10-06
期刊：
影响因子：
64.8
通讯作者：
JULIUS, D
中科院分区：
文献类型：
--
作者：
BRAKE, AJ;WAGENBACH, MJ;JULIUS, D
腺苷-5'-三磷酸腺苷（ATP）分子是神经和非神经组织中的细胞外信使，它激活几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(1)。atp门控通道（称为P-2X受体）在平滑肌细胞和自主神经和感觉神经元上具有特征，它们介导膜去极化，在某些情况下介导Ca2+进入(2)。P-2X受体在功能上是异质的，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血清素门控通道。我们在这里报道，尽管如此接近的功能相似性，克隆的P-2X受体的推断序列预测一个不寻常的亚基结构类似于电压不敏感的阳离子通道。因此，P-2X受体提供了一个显著的趋同进化的例子，即从具有非常不同结构特征的亚基中形成具有相似功能特性的蛋白质。ATP受体与RP-2基因序列相似，RP-2基因在胸腺细胞程序化过程中被激活。(3)死亡。RP-2可能编码ATP或其他代谢产物在细胞凋亡过程中释放的受体。
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(1). ATP-gated channels (termed P-2X receptors) have been characterized on smooth muscle cells and autonomic and sensory neurons, where they mediate membrane depolarization and, in some cases, Ca2+ entry(2). P-2X 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 P-2X receptor predicts an unusual subunit structure resembling voltage-insensitive cation channels. Thus, the P-2X 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(3). RP-2 may encode a receptor for ATP or another metabolite released during apoptosis.