Ligand recognition and G protein coupling of the human itch receptor MRGPRX1.
Autor: | Guo L; Advanced Medical Research Institute, Cheeloo College of Medicine, Shandong University, Jinan, China.; Key Laboratory of Experimental Teratology of the Ministry of Education, Department of Biochemistry and Molecular Biology, Shandong University School of Medicine, Jinan, China., Zhang Y; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.; School of Life Science and Technology, ShanghaiTech University, Shanghai, 201210, China., Fang G; Key Laboratory Experimental Teratology of the Ministry of Education and Department of Physiology, School of Basic Medical Sciences, Shandong University, Jinan, Shandong, China., Tie L; Department of Pharmacology, School of Basic Medical Sciences, Peking University and Beijing Key Laboratory of Tumor Systems Biology, Peking University, Beijing, China., Zhuang Y; Key Laboratory Experimental Teratology of the Ministry of Education and Department of Physiology, School of Basic Medical Sciences, Shandong University, Jinan, Shandong, China., Xue C; Department of Immunology and Microbiology, Southern University of Science and Technology, Shenzhen, Guangdong, China., Liu Q; Advanced Medical Research Institute, Cheeloo College of Medicine, Shandong University, Jinan, China., Zhang M; Key Laboratory of Experimental Teratology of the Ministry of Education, Department of Biochemistry and Molecular Biology, Shandong University School of Medicine, Jinan, China., Zhu K; Key Laboratory of Experimental Teratology of the Ministry of Education, Department of Biochemistry and Molecular Biology, Shandong University School of Medicine, Jinan, China., You C; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China., Xu P; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China., Yuan Q; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China., Zhang C; Key Laboratory of Experimental Teratology of the Ministry of Education, Department of Biochemistry and Molecular Biology, Shandong University School of Medicine, Jinan, China., Liu L; Advanced Medical Research Institute, Cheeloo College of Medicine, Shandong University, Jinan, China., Rong N; Key Laboratory of Experimental Teratology of the Ministry of Education, Department of Biochemistry and Molecular Biology, Shandong University School of Medicine, Jinan, China., Peng S; Advanced Medical Research Institute, Cheeloo College of Medicine, Shandong University, Jinan, China., Liu Y; Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China., Wang C; Advanced Medical Research Institute, Cheeloo College of Medicine, Shandong University, Jinan, China., Luo X; Advanced Medical Research Institute, Cheeloo College of Medicine, Shandong University, Jinan, China., Lv Z; Advanced Medical Research Institute, Cheeloo College of Medicine, Shandong University, Jinan, China., Kang D; Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Jinan, China., Yu X; Key Laboratory Experimental Teratology of the Ministry of Education and Department of Physiology, School of Basic Medical Sciences, Shandong University, Jinan, Shandong, China., Zhang C; Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China., Jiang Y; Lingang Laboratory, Shanghai, China., Dong X; The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Zhou J; Department of Pharmacology, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China. zhoujiuyao@tom.com., Liu Z; Department of Immunology and Microbiology, Southern University of Science and Technology, Shenzhen, Guangdong, China. liuzm@sustech.edu.cn., Yang F; Advanced Medical Research Institute, Cheeloo College of Medicine, Shandong University, Jinan, China. yangfan1357@163.com.; Key Laboratory Experimental Teratology of the Ministry of Education and Department of Physiology, School of Basic Medical Sciences, Shandong University, Jinan, Shandong, China. yangfan1357@163.com., Eric Xu H; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China. eric.xu@simm.ac.cn., Sun JP; Advanced Medical Research Institute, Cheeloo College of Medicine, Shandong University, Jinan, China. sunjinpeng@sdu.edu.cn.; Key Laboratory of Experimental Teratology of the Ministry of Education, Department of Biochemistry and Molecular Biology, Shandong University School of Medicine, Jinan, China. sunjinpeng@sdu.edu.cn.; Department of Pharmacology, School of Basic Medical Sciences, Peking University and Beijing Key Laboratory of Tumor Systems Biology, Peking University, Beijing, China. sunjinpeng@sdu.edu.cn. |
---|---|
Jazyk: | angličtina |
Zdroj: | Nature communications [Nat Commun] 2023 Aug 17; Vol. 14 (1), pp. 5004. Date of Electronic Publication: 2023 Aug 17. |
DOI: | 10.1038/s41467-023-40705-z |
Abstrakt: | 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 G 6.48 XP 6.50 F 6.51 G 6.52 X (© 2023. Springer Nature Limited.) |
Databáze: | MEDLINE |
Externí odkaz: |