| 题名 | Ligand recognition and G protein coupling of the human itch receptor MRGPRX1 |
| 作者 | Guo，Lulu1,2; Zhang，Yumu3,4; Fang，Guoxing5; Tie，Lu6; Zhuang，Yuming5; Xue，Chenyang7  ; Liu，Qi1; Zhang，Minghui2; Zhu，Kongkai2; You，Chongzhao3; Xu，Peiyu3; Yuan，Qingning3; Zhang，Chao2; Liu，Lei1; Rong，Naikang2; Peng，Shengxuan1; Liu，Yuan8; Wang，Chuanzheng1; Luo，Xin1; Lv，Zongyao1; Kang，Dongwei9; Yu，Xiao5; Zhang，Cheng8; Jiang，Yi10; Dong，Xinzhong11,12; Zhou，Jiuyao13 ; Liu，Zhongmin7; Yang，Fan1,5; Eric Xu，H.3; Sun，Jin Peng1,2,6
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| 通讯作者 | Zhou，Jiuyao; Liu，Zhongmin; Yang，Fan; Eric Xu，H.; Sun，Jin Peng |
| 发表日期 | 2023-12-01
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| DOI | |
| 发表期刊 | |
| EISSN | 2041-1723
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| 卷号 | 14期号:1 |
| 摘要 | MRGPRX1, a Mas-related GPCR (MRGPR), is a key receptor for itch perception and targeting MRGPRX1 may have potential to treat both chronic itch and pain. Here we report cryo-EM structures of the MRGPRX1-Gi1 and MRGPRX1-Gq trimers in complex with two peptide ligands, BAM8-22 and CNF-Tx2. These structures reveal a shallow orthosteric pocket and its conformational plasticity for sensing multiple different peptidic itch allergens. Distinct from MRGPRX2, MRGPRX1 contains a unique pocket feature at the extracellular ends of TM3 and TM4 to accommodate the peptide C-terminal “RF/RY” motif, which could serve as key mechanisms for peptidic allergen recognition. Below the ligand binding pocket, the GXPFGXF/W motif is essential for the inward tilting of the upper end of TM6 to induce receptor activation. Moreover, structural features inside the ligand pocket and on the cytoplasmic side of MRGPRX1 are identified as key elements for both Gi and Gq signaling. Collectively, our studies provide structural insights into understanding itch sensation, MRGPRX1 activation, and downstream G protein signaling. |
| 相关链接 | [Scopus记录] |
| 收录类别 | |
| 语种 | 英语
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| 重要成果 | NI论文
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| 学校署名 | 通讯
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| 资助项目 | China National Funds for Distinguished Young Scientists[81825022]
; National Natural Science Foundation of China-Yunnan Joint Fund[91939301]
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| WOS研究方向 | Science & Technology - Other Topics
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| WOS类目 | Multidisciplinary Sciences
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| WOS记录号 | WOS:001067877800033
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| 出版者 | |
| Scopus记录号 | 2-s2.0-85168269576
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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/559434 |
| 专题 | 生命科学学院_基础免疫与微生物学系 生命科学学院 |
| 作者单位 | 1.Advanced Medical Research Institute,Cheeloo College of Medicine,Shandong University,Jinan,China 2.Key Laboratory of Experimental Teratology of the Ministry of Education,Department of Biochemistry and Molecular Biology,Shandong University School of Medicine,Jinan,China 3.State Key Laboratory of Drug Research,Shanghai Institute of Materia Medica,Chinese Academy of Sciences,Shanghai,China 4.School of Life Science and Technology,ShanghaiTech University,Shanghai,201210,China 5.Key Laboratory Experimental Teratology of the Ministry of Education and Department of Physiology,School of Basic Medical Sciences,Shandong University,Jinan,Shandong,China 6.Department of Pharmacology,School of Basic Medical Sciences,Peking University and Beijing Key Laboratory of Tumor Systems Biology,Peking University,Beijing,China 7.Department of Immunology and Microbiology,Southern University of Science and Technology,Shenzhen,Guangdong,China 8.Qilu Hospital,Cheeloo College of Medicine,Shandong University,Jinan,Shandong,China 9.Department of Medicinal Chemistry,Key Laboratory of Chemical Biology (Ministry of Education),School of Pharmaceutical Sciences,Shandong University,Jinan,China 10.Lingang Laboratory,Shanghai,China 11.The Solomon H. Snyder Department of Neuroscience,Johns Hopkins University School of Medicine,Baltimore,United States 12.Howard Hughes Medical Institute,Johns Hopkins University School of Medicine,Baltimore,United States 13.Department of Pharmacology,School of Pharmaceutical Sciences,Guangzhou University of Chinese Medicine,Guangzhou,China |
| 通讯作者单位 | 基础免疫与微生物学系 |
| 推荐引用方式 GB/T 7714 |
Guo，Lulu,Zhang，Yumu,Fang，Guoxing,et al. Ligand recognition and G protein coupling of the human itch receptor MRGPRX1[J]. Nature Communications,2023,14(1).
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| APA |
Guo，Lulu.,Zhang，Yumu.,Fang，Guoxing.,Tie，Lu.,Zhuang，Yuming.,...&Sun，Jin Peng.(2023).Ligand recognition and G protein coupling of the human itch receptor MRGPRX1.Nature Communications,14(1).
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| MLA |
Guo，Lulu,et al."Ligand recognition and G protein coupling of the human itch receptor MRGPRX1".Nature Communications 14.1(2023).
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| 条目包含的文件 | ||||||
| 文件名称/大小 | 文献类型 | 版本类型 | 开放类型 | 使用许可 | 操作 | |
| 代表性论文 1c.pdf（3463KB） | 期刊论文 | 作者接受稿 | 开放获取 | CC BY-NC-SA | 浏览 | |
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