Structural basis for human Cav1.2 inhibition by multiple drugs and the neurotoxin calciseptineCav1.2 channels play crucial roles in various neuronal and physiological processes. Here, we present cryo-EM structures of human Cav1.2, both in its apo form and in complex with several drugs, as well as the peptide neurotoxin calciseptine. Most structures, apo or bound to calciseptine, amlodipine, or a combination of amiodarone and sofosbuvir, exhibit a consistent inactivated conformation with a sealed gate, three up voltage-sensing domains (VSDs), and a down VSDII. Calciseptine sits on the shoulder of the pore domain, away from the permeation path.Cav1.2 channels play crucial roles in various neuronal and physiological processes. Here, we present cryo-EM structures of human Cav1.2, both in its apo form and in complex with several drugs, as well as the peptide neurotoxin calciseptine. Most structures, apo or bound to calciseptine, amlodipine, or a combination of amiodarone and sofosbuvir, exhibit a consistent inactivated conformation with a sealed gate, three up voltage-sensing domains (VSDs), and a down VSDII. Calciseptine sits on the shoulder of the pore domain, away from the permeation path.Shuai Gao, Xia Yao, Jiaofeng Chen, Gaoxingyu Huang, Xiao Fan, Lingfeng Xue, Zhangqiang Li, Tong Wu, Yupeng Zheng, Jian Huang, Xueqin Jin, Yan Wang, Zhifei Wang, Yong Yu, Lei Liu, Xiaojing Pan, Chen Song, Nieng Yanhttps://www.cell.com/cell/fulltext/S0092-8674(23)01106-6?rss=yeshttp://www.cell.com/cell/inpress.rssCellCell RSS feed.Wireless News CampaignNovember 16, 2023

Powered by WPeMatico