| Title | Ligand recognition and G protein coupling of the human itch receptor MRGPRX1 |
| Author | 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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| Corresponding Author | Zhou，Jiuyao; Liu，Zhongmin; Yang，Fan; Eric Xu，H.; Sun，Jin Peng |
| Publication Years | 2023-12-01
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| DOI | |
| Source Title | |
| EISSN | 2041-1723
|
| Volume | 14Issue:1 |
| Abstract | 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. |
| URL | [Source Record] |
| Indexed By | |
| Language | English
|
| Important Publications | NI Journal Papers
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| SUSTech Authorship | Corresponding
|
| Funding Project | China National Funds for Distinguished Young Scientists[81825022]
; National Natural Science Foundation of China-Yunnan Joint Fund[91939301]
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| WOS Research Area | Science & Technology - Other Topics
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| WOS Subject | Multidisciplinary Sciences
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| WOS Accession No | WOS:001067877800033
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| Publisher | |
| Scopus EID | 2-s2.0-85168269576
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| Data Source | Scopus
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| Citation statistics |
Cited Times [WOS]:0
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| Document Type | Journal Article |
| Identifier | http://kc.sustech.edu.cn/handle/2SGJ60CL/559434 |
| Department | Department of Immunology and Microbiology 生命科学学院 |
| Affiliation | 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 |
| Corresponding Author Affilication | Department of Immunology and Microbiology |
| Recommended Citation 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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