Cryo-EM structure of human heptameric pannexin 2 channel.
Cryo-EM structure of human heptameric pannexin 2 channel.
复制标题
DOI：
10.1038/s41467-023-36861-x
复制
发表时间：
2023-03-03
影响因子：
16.6
通讯作者：
Zhang, Huawei
中科院分区：
文献类型：
--
作者：
Zhang, Hang;Wang, Shiyu;Zhang, Zhenzhen;Hou, Mengzhuo;Du, Chunyu;Zhao, Zhenye;Vogel, Horst;Li, Zhifang;Yan, Kaige;Zhang, Xiaokang;Lu, Jianping;Liang, Yujie;Yuan, Shuguang;Wang, Daping;Zhang, Huawei
Pannexin 2 (Panx2) is a large-pore ATP-permeable channel with critical roles in various physiological processes, such as the inflammatory response, energy production and apoptosis. Its dysfunction is related to numerous pathological conditions including ischemic brain injury, glioma and glioblastoma multiforme. However, the working mechanism of Panx2 remains unclear. Here, we present the cryo-electron microscopy structure of human Panx2 at a resolution of 3.4 Å. Panx2 structure assembles as a heptamer, forming an exceptionally wide channel pore across the transmembrane and intracellular domains, which is compatible with ATP permeation. Comparing Panx2 with Panx1 structures in different states reveals that the Panx2 structure corresponds to an open channel state. A ring of seven arginine residues located at the extracellular entrance forms the narrowest site of the channel, which serves as the critical molecular filter controlling the permeation of substrate molecules. This is further verified by molecular dynamics simulations and ATP release assays. Our studies reveal the architecture of the Panx2 channel and provide insights into the molecular mechanism of its channel gating. Pannexin 2 plays critical roles in many physiological processes but its mechanism remain unclear. Here, authors report the cryo-EM structure of human Panx2 in the open state and identify critical residues for its gating.
登录
查看更多内容
影响因子：
64.8
作者：
Jumper J;Evans R;Pritzel A;Green T;Figurnov M;Ronneberger O;Tunyasuvunakool K;Bates R;Žídek A;Potapenko A;Bridgland A;Meyer C;Kohl SAA;Ballard AJ;Cowie A;Romera-Paredes B;Nikolov S;Jain R;Adler J;Back T;Petersen S;Reiman D;Clancy E;Zielinski M;Steinegger M;Pacholska M;Berghammer T;Bodenstein S;Silver D;Vinyals O;Senior AW;Kavukcuoglu K;Kohli P;Hassabis D
通讯作者：
Hassabis D
影响因子：
2.9
作者：
Jacobson, MP;Pincus, DL;Friesner, RA
通讯作者：
Friesner, RA
通过分子间精氨酸-精氨酸吸引力构建耐热多孔虾铁蛋白晶体以进行分子封装
影响因子：
8.8
作者：
Chen, Hai;Zhang, Tuo;Zhao, Guanghua
通讯作者：
Zhao, Guanghua
DOI：
10.1073/pnas.2233464100
发表时间：
2003-11-11
影响因子：
11.1
作者：
Bruzzone, R;Hormuzdi, SG;Monyer, H
通讯作者：
Monyer, H
影响因子：
3.6
作者：
Beckmann, Anja;Grissmer, Alexander;Meier, Carola
通讯作者：
Meier, Carola