Department of Molecular Medicine, Cornell University, Ithaca, NY, 14853, USA.
Adv Exp Med Biol. 2017;1051:55-69. doi: 10.1007/5584_2017_55.
Extracellular ATP-gated P2X receptors are trimeric non-selective cation channels important for many physiological events including immune response and neural transmission. These receptors belong to a unique class of ligand-gated ion channels composed of only six transmembrane helices and a relatively small extracellular domain that harbors three ATP-binding pockets. The crystal structures of P2X receptors, including the recent P2X3 structures representing three different stages of the gating cycle, have provided a compelling structural foundation for understanding how this class of ligand-gated ion channels function. These structures, in combination with numerous functional studies ranging from classic mutagenesis and electrophysiology to modern optogenetic pharmacology, have uncovered unique molecular mechanisms of P2X receptor function. This review article summarizes the current knowledge in P2X receptor activation, especially focusing on the mechanisms underlying ATP-binding, conformational changes in the extracellular domain, and channel gating and desensitization.
细胞外 ATP 门控 P2X 受体是三聚体非选择性阳离子通道，对于许多生理事件（包括免疫反应和神经传递）都很重要。这些受体属于一种独特的配体门控离子通道家族，仅由六个跨膜螺旋和一个相对较小的含有三个 ATP 结合口袋的细胞外结构域组成。P2X 受体的晶体结构，包括最近代表门控循环三个不同阶段的 P2X3 结构，为理解这类配体门控离子通道的功能提供了令人信服的结构基础。这些结构，结合从经典诱变和电生理学到现代光遗传药理学的众多功能研究，揭示了 P2X 受体功能的独特分子机制。本文综述了 P2X 受体激活的最新知识，特别侧重于 ATP 结合、细胞外结构域构象变化以及通道门控和脱敏的机制。
