Single-molecule force spectroscopy study of interactions between angiotensin II type 1 receptor and different biased ligands in living cells
文献类型：期刊论文
| 作者 | Li, Wenhui1,2; Xu, Jiachao1,2; Kou, Xiaolong1,2; Zhao, Rong1,2; Zhou, Wei1,2; Fang, Xiaohong1,2 |
| 刊名 | ANALYTICAL AND BIOANALYTICAL CHEMISTRY
 |
| 出版日期 | 2018-05-01 |
| 卷号 | 410期号:14页码:3275-3284 |
| ISSN号 | 1618-2642 |
| 关键词 | Angiotensin Ii Type 1 Receptor Biased Ligands Atomic Force Microscopy Single-molecule Force Spectroscopy Energy Landscape |
| DOI | 10.1007/s00216-018-0956-3 |
| 英文摘要 | Angiotensin II type 1 receptor (AT1R), a typical G protein-coupled receptor, plays a key role in regulating many cardiovascular functions. Different ligands can bind with AT1R to selectively activate either G protein (Gq) or beta-arrestin (beta-arr) pathway, or both pathways, but the molecular mechanism is not clear yet. In this work, we used, for the first time, atomic force microscopy-based single molecule force spectroscopy (SMFS) to study the interactions of AT1R with three types of ligands, balanced ligand, Gq-biased ligand, and beta-arr-biased ligand, in living cells. The results revealed their difference in binding force and binding stability. The complex of the Gq-biased ligand-AT1R overcame two energy barriers with an intermediate state during dissociation, whereas that of beta-arr-biased ligand-AT1R complex overcame one energy barrier. This indicated that AT1R had different ligand-binding conformational substates and underwent different structural changes to activate downstream signaling pathways with variable agonist efficacies. Quantitative analysis of AT1R-ligand binding in living cells at the single-molecule level offers a new tool to study the molecular mechanism of AT1R biased activation. |
| 语种 | 英语 |
| 出版者 | SPRINGER HEIDELBERG |
| WOS记录号 | WOS:000431401000008 |
| 源URL | [http://ir.iccas.ac.cn/handle/121111/43119]  |
| 专题 | 中国科学院化学研究所 |
| 通讯作者 | Fang, Xiaohong |
| 作者单位 | 1.Chinese Acad Sci, Beijing Natl Lab Mol Sci, Inst Chem, Key Lab Mol Nanostruct & Nanotechnol, 2 North First St, Beijing 100190, Peoples R China 2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China |
| 推荐引用方式 GB/T 7714 | Li, Wenhui,Xu, Jiachao,Kou, Xiaolong,et al. Single-molecule force spectroscopy study of interactions between angiotensin II type 1 receptor and different biased ligands in living cells[J]. ANALYTICAL AND BIOANALYTICAL CHEMISTRY,2018,410(14):3275-3284. |
| APA | Li, Wenhui,Xu, Jiachao,Kou, Xiaolong,Zhao, Rong,Zhou, Wei,&Fang, Xiaohong.(2018).Single-molecule force spectroscopy study of interactions between angiotensin II type 1 receptor and different biased ligands in living cells.ANALYTICAL AND BIOANALYTICAL CHEMISTRY,410(14),3275-3284. |
| MLA | Li, Wenhui,et al."Single-molecule force spectroscopy study of interactions between angiotensin II type 1 receptor and different biased ligands in living cells".ANALYTICAL AND BIOANALYTICAL CHEMISTRY 410.14(2018):3275-3284. |
入库方式： OAI收割
来源：化学研究所
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