Bo Yu, Qiuyuan Lu, Jian Li, Xinyu Cheng, Han Hu, Yuanshuo Li, Tong Che, Yaoguang Hua, Haihai Jiang, Yuting Zhang, Cuiling Xian, Tingting Yang, Ying Fu, Yixiang Chen, Weiwei Nan, Peter J McCormick, Bing Xiong, Jingjing Duan, Bo Zeng, Yanyan Li, Yang Fu, Jin Zhang
HCN channels are important for regulating heart rhythm and nerve activity and have been studied as potential drug targets for treating depression, arrhythmia, nerve pain and epilepsy.Despite possessing unique pharmacological properties, HCN channels share common characteristics in that they are activated by hyperpolarization and modulated by cAMP and other membrane lipids. However, the mechanisms of how these ligands bind and modulate HCN channels are unclear. In this study, we solved structures of full-length human HCN3 using cryo-EM and captured two different states, including a state without any ligand bound and a state with cAMP bound...
April 16, 2024: Journal of Biological Chemistry