| 题名 | Cryo-EM structure of human HCN3 channel and its regulation by cAMP |
| 作者 | Yu，Bo1,2; Lu，Qiuyuan3  ; Li，Jian4; Cheng，Xinyu1,2; Hu，Han5; Li，Yuanshuo5; Che，Tong1,2; Hua，Yaoguang1,2; Jiang，Haihai1,2; Zhang，Yuting5; Xian，Cuiling5; Yang，Tingting1,2; Fu，Ying1,2; Chen，Yixiang1,2; Nan，Weiwei1,2; McCormick，Peter J.6; Xiong，Bing7; Duan，Jingjing8; Zeng，Bo9; Li，Yanyan10,11 ; Fu，Yang3; Zhang，Jin1,2
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| 通讯作者 | Li，Yanyan; Fu，Yang; Zhang，Jin |
| 共同第一作者 | Yu，Bo; Lu，Qiuyuan; Li，Jian; Cheng，Xinyu |
| 发表日期 | 2024-06-01
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| DOI | |
| 发表期刊 | |
| ISSN | 0021-9258
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| EISSN | 1083-351X
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| 卷号 | 300期号:6 |
| 摘要 | 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. Our structures reveal the novel binding sites for cholesteryl hemisuccinate in apo state and show how cholesteryl hemisuccinate and cAMP binding cause conformational changes in different states. These findings explain how these small modulators are sensed in mammals at the molecular level. The results of our study could help to design more potent and specific compounds to influence HCN channel activity and offer new therapeutic possibilities for diseases that lack effective treatment. |
| 关键词 | |
| 相关链接 | [Scopus记录] |
| 收录类别 | |
| 语种 | 英语
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| 学校署名 | 共同第一
; 通讯
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| ESI学科分类 | BIOLOGY & BIOCHEMISTRY
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| Scopus记录号 | 2-s2.0-85192940740
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| 来源库 | Scopus
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| 引用统计 |
被引频次[WOS]：2
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| 成果类型 | 期刊论文 |
| 条目标识符 | http://sustech.caswiz.com/handle/2SGJ60CL/761068 |
| 专题 | 南方科技大学医学院 生命科学学院_化学生物学系 |
| 作者单位 | 1.The MOE Basic Research and Innovation Center for the Targeted Therapeutics of Solid Tumors,School of Basic Medical Sciences,Jiangxi Medical College,Nanchang University,Nanchang,China 2.The Second Affiliated Hospital,Jiangxi Medical College,Nanchang University,Nanchang,China 3.School of Medicine,Southern University of Science and Technology,Shenzhen,Guangdong,China 4.College of Pharmacy,Gannan Medical University,Ganzhou,China 5.Shenzhen Crystalo Biopharmaceutical Co,Ltd,Shenzhen,Guangdong,China 6.William Harvey Research Institute,Bart's and The London School of Medicine and Dentistry,Queen Mary University of London,London,United Kingdom 7.Department of Medicinal Chemistry,Shanghai Institute of Materia Medica,Chinese Academy of Sciences,Shanghai,China 8.Human Aging Research Institute (HARI),School of Life Sciences,Nanchang University,Nanchang,Jiangxi,China 9.Key Laboratory of Medical Electrophysiology,Ministry of Education & Medical Electrophysiological Key Laboratory of Sichuan Province,Institute of Cardiovascular Research,Southwest Medical University,Luzhou,Sichuan,China 10.Department of Chemical Biology,School of Life Southern University of Science and Technology,Southern University of Science and Technology,Shenzhen,Guangdong,China 11.Institute for Biological Electron Microscopy,Southern University of Science and Technology,Shenzhen,Guangdong,China |
| 通讯作者单位 | 化学生物学系; 南方科技大学; 南方科技大学医学院 |
| 推荐引用方式 GB/T 7714 |
Yu，Bo,Lu，Qiuyuan,Li，Jian,et al. Cryo-EM structure of human HCN3 channel and its regulation by cAMP[J]. Journal of Biological Chemistry,2024,300(6).
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| APA |
Yu，Bo.,Lu，Qiuyuan.,Li，Jian.,Cheng，Xinyu.,Hu，Han.,...&Zhang，Jin.(2024).Cryo-EM structure of human HCN3 channel and its regulation by cAMP.Journal of Biological Chemistry,300(6).
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| MLA |
Yu，Bo,et al."Cryo-EM structure of human HCN3 channel and its regulation by cAMP".Journal of Biological Chemistry 300.6(2024).
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| 条目包含的文件 | 条目无相关文件。 | |||||
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