| 论文题目: | Mechanism of Ligand Activation of a Eukaryotic Cyclic Nucleotide-Gated Channel |
| 作者: | Xiangdong Zheng, Ziao Fu, Deyuan Su, Yuebin Zhang, Minghui Li, Yaping Pan, Huan Li, Shufang Li, Robert A. Grassucci, Zhenning Ren, Zhengshan Hu, Xueming Li, Ming Zhou, Guohui Li, Joachim Frank & Jian Yang |
| 联系作者: | jy160@columbia.edu |
| 发表年度: | 2020 |
| DOI: | doi: 10.1038/s41594-020-0433-5 |
| 摘要: | Cyclic nucleotide-gated (CNG) channels convert cyclic nucleotide (CN) binding and unbinding into electrical signals in sensory receptors and neurons. The molecular conformational changes underpinning ligand activation are largely undefined. We report both closed- and open-state atomic cryo-EM structures of a full-length Caenorhabditis elegans cyclic GMP-activated channel TAX-4, reconstituted in lipid nanodiscs. These structures, together with computational and functional analyses and a mutant channel structure, reveal a double-barrier hydrophobic gate formed by two S6 amino acids in the central cavity. cGMP binding produces global conformational changes that open the cavity gate located ~52 ？ away but do not alter the structure of the selectivity filter-the commonly presumed activation gate. Our work provides mechanistic insights into the allosteric gating and regulation of CN-gated and nucleotide-modulated channels and CNG channel-related channelopathies |
| 刊物名称: | Nature Structural & Molecular Biology |
| 论文出处: | https://www.nature.com/articles/s41594-020-0433-5 |
| 影响因子: | 11.875(2018年) |
