Atomic Level Characterization of the Nonproton Ligand-sensing Domain of ASIC3 Channels
文献类型：期刊论文
| 作者 | Yu, Ye ; Li, Wei-Guang ; Chen, Zhi ; Cao, Hui ; Yang, Huaiyu ; Jiang, Hualiang ; Xu, Tian-Le(徐天乐) |
| 刊名 | JOURNAL OF BIOLOGICAL CHEMISTRY
 |
| 出版日期 | 2011 |
| 卷号 | 286期号:28页码:24996-25006 |
| 关键词 | ION-CHANNEL MOLECULAR-DYNAMICS EXTRACELLULAR DOMAIN NEURONS PORE 1A DESENSITIZATION ION-CHANNEL-1 MODULATION ACIDOSIS |
| ISSN号 | 0021-9258 |
| 通讯作者 | Jiang, HL (reprint author), 555 Zu Chong Zhi Rd,Zhang Jiang Hi Tech Pk, Shanghai 201203, Peoples R China,hljiang@mail.shcnc.ac.cn |
| 英文摘要 | Acid-sensing ion channels (ASICs) are known to be primarily activated by extracellular protons. Recently, we characterized a novel nonproton ligand (2-guanidine-4-methylquinazoline, GMQ), which activates the ASIC3 channel subtype at neutral pH. Using an interactive computational-experimental approach, here we extend our investigation to delineate the architecture of the GMQ-sensing domain in the ASIC3 channels. We first established a GMQ binding mode and revealed that residues Glu-423, Glu-79, Leu-77, Arg-376, Gln-271, and Gln-269 play key roles in forming the GMQ-sensing domain. We then verified the GMQ binding mode using ab initio calculation and mutagenesis and demonstrated the critical role of the above GMQ-binding residues in the interplay among GMQ, proton, and Ca(2+) in regulating the function of ASIC3. Additionally, we showed that the same residues involved in coordinating GMQ responses are also critical for activation of the ASIC3(E79C) mutant by thiol-reactive compound DTNB. Thus, a range of complementary techniques provide independent evidence for the structural details of the GMQ-sensing domain at atomic level, laying the foundation for further investigations of endogenous nonproton ligands and gating mechanisms of the ASIC3 channels. |
| 学科主题 | Biochemistry & Molecular Biology |
| 收录类别 | SCI |
| 资助信息 | National Natural Science Foundation of China[30830035, 9091300]; National Basic Research Program of China[2011CBA00408]; Shanghai Municipal Government[09XD1404900]; Sanofi-Aventis-Shanghai Institutes for Biological Sciences |
| 语种 | 英语 |
| 公开日期 | 2012-07-13 |
| 源URL | [http://ir.sibs.ac.cn/handle/331001/1533]  |
| 专题 | 上海神经科学研究所_神经所(总) |
| 推荐引用方式 GB/T 7714 | Yu, Ye,Li, Wei-Guang,Chen, Zhi,et al. Atomic Level Characterization of the Nonproton Ligand-sensing Domain of ASIC3 Channels[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2011,286(28):24996-25006. |
| APA | Yu, Ye.,Li, Wei-Guang.,Chen, Zhi.,Cao, Hui.,Yang, Huaiyu.,...&Xu, Tian-Le.(2011).Atomic Level Characterization of the Nonproton Ligand-sensing Domain of ASIC3 Channels.JOURNAL OF BIOLOGICAL CHEMISTRY,286(28),24996-25006. |
| MLA | Yu, Ye,et al."Atomic Level Characterization of the Nonproton Ligand-sensing Domain of ASIC3 Channels".JOURNAL OF BIOLOGICAL CHEMISTRY 286.28(2011):24996-25006. |
入库方式： OAI收割
来源：上海神经科学研究所
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