Tsuyama Taiichi, Teramura Ryuga, Mitsuoka Kaoru, Kishikawa Jun-Ichi, Yokoyama Ken
Department of Molecular Biosciences, Kyoto Sangyo University, Kamigamo-Motoyama, Kita-ku, Kyoto, 603-8555, Japan.
Research Center for Ultra-High Voltage Electron Microscopy, Osaka University, Osaka, Japan.
Biochem Biophys Res Commun. 2025 Jan;745:151227. doi: 10.1016/j.bbrc.2024.151227. Epub 2024 Dec 20.
Pannexin-3 (PANX3) is a member of the pannexin family of large-pore, ATP-permeable channels conserved across vertebrates. PANX3 contributes to various developmental and pathophysiological processes by permeating ATP and Ca ions; however, the structural basis of PANX3 channel function remains unclear. Here, we present the cryo-EM structure of human PANX3 at 2.9-3.2 Å. The PANX3 channel is heptameric and forms a transmembrane pore along the central symmetric axis. The narrowest constriction of the pore is composed of an isoleucine ring located in the extracellular region, and its size is comparable to that of other pannexins. A structural variability analysis revealed prominent structural dynamics in intracellular regions. Our structural studies provide a foundation for understanding the detailed properties of pannexin channels.
泛连接蛋白3（PANX3）是大孔、ATP可渗透通道的泛连接蛋白家族成员，在脊椎动物中保守存在。PANX3通过使ATP和钙离子通透，参与各种发育和病理生理过程；然而，PANX3通道功能的结构基础仍不清楚。在此，我们展示了人PANX3在2.9 - 3.2 Å分辨率下的冷冻电镜结构。PANX3通道是七聚体，沿中心对称轴形成跨膜孔。孔的最窄收缩处由位于细胞外区域的异亮氨酸环组成，其大小与其他泛连接蛋白相当。结构变异性分析揭示了细胞内区域显著的结构动力学。我们的结构研究为理解泛连接蛋白通道的详细特性提供了基础。
