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Crystal structure of the human 5-HT1B serotonin receptor bound to an inverse agonist 期刊论文

编号：

28da5aa7-04e8-4f5a-b718-8462b0fc0f44
作者：

Yin, Wanchao^[1,2,3,4] Zhou, X. Edward^[1,4] Yang, Dehua^[3,5] de Waal, Parker W.^[4] Wang, Meitian^[6] Dai, Antao^[3,5] Cai, Xiaoqing^[3,5] Huang, ChiaYing^[6] Liu, Ping^[1] Wang, Xiaoxi^[1] Yin, Yanting^[1,4] Liu, Bo^[1] Zhou, Yu^[7] Wang, Jiang^[7] Liu, Hong^[7] Caffrey, Martin^[8,9,10] Melcher, Karsten^[4] Xu, Yechun^[3] Wang, MingWei^[3,5,11,12] Xu, H. Eric^[1,4] Jiang, Yi^[1,4]
语种：

English
期刊：

CELL DISCOVERY ISSN：2056-5968 2018 年 4 卷 ; MAR 13
收录：
摘要：

5-hydroxytryptamine (5-HT, also known as serotonin) regulates many physiological processes through the 5-HT receptor family. Here we report the crystal structure of 5-HT1B subtype receptor (5-HT1BR) bound to the psychotropic serotonin receptor inverse agonist methiothepin (MT). Crystallization was facilitated by replacing ICL3 with a novel optimized variant of BRIL (OB1) that enhances the formation of intermolecular polar interactions, making OB1 a potential useful tool for structural studies of membrane proteins. Unlike the agonist ergotamine (ERG), MT occupies only the conserved orthosteric binding pocket, explaining the wide spectrum effect of MT on serotonin receptors. Compared with ERG, MT shifts toward TM6 and sterically pushes residues W327(6.48), F330(6.50) and F331(6.51) from inside the orthosteric binding pocket, leading to an outward movement of the extracellular end and a corresponding inward shift of the intracellular end of TM6, a feature shared by other reported inactive G protein-coupled receptor (GPCR) structures. Together with the previous agonist-bound serotonin receptor structures, the inverse agonist-bound 5-HT1BR structure identifies a basis for the ligand-mediated switch of 5-HT1BR activity and provides a structural understanding of the inactivation mechanism of 5-HT1BR and some other class A GPCRs, characterized by ligand-induced outward movement of the extracellular end of TM6 that is coupled with inward movement of the cytoplasmic end of this helix.
推荐引用方式
GB/T 7714：

Yin Wanchao,Zhou X. Edward,Yang Dehua, et al. Crystal structure of the human 5-HT1B serotonin receptor bound to an inverse agonist [J].CELL DISCOVERY,2018,4.
APA：

Yin Wanchao,Zhou X. Edward,Yang Dehua,de Waal Parker W.,&Jiang Yi.(2018).Crystal structure of the human 5-HT1B serotonin receptor bound to an inverse agonist .CELL DISCOVERY,4.
MLA：

Yin Wanchao, et al. "Crystal structure of the human 5-HT1B serotonin receptor bound to an inverse agonist" .CELL DISCOVERY 4(2018).
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