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Ligand recognition, unconventional activation, and G protein coupling of the prostaglandin E2 receptor EP2 subtype.
Qu, Changxiu; Mao, Chunyou; Xiao, Peng; Shen, Qingya; Zhong, Ya-Ni; Yang, Fan; Shen, Dan-Dan; Tao, Xiaona; Zhang, Huibing; Yan, Xu; Zhao, Ru-Jia; He, Junyan; Guan, Ying; Zhang, Chao; Hou, Guihua; Zhang, Peng-Ju; Hou, Guige; Li, Zijian; Yu, Xiao; Chai, Ren-Jie; Guan, You-Fei; Sun, Jin-Peng; Zhang, Yan.
Afiliación
  • Qu C; Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing 100191, China.
  • Mao C; Key Laboratory Experimental Teratology of the Ministry of Education and Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Cheeloo college of Medicine, Shandong University, Jinan, Shandong 250012, China.
  • Xiao P; Department of Biophysics and Department of Pathology of Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China.
  • Shen Q; Liangzhu Laboratory, Zhejiang University Medical Center, 1369 West Wenyi Road, Hangzhou 311121, China.
  • Zhong YN; Key Laboratory Experimental Teratology of the Ministry of Education and Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Cheeloo college of Medicine, Shandong University, Jinan, Shandong 250012, China.
  • Yang F; Department of Biophysics and Department of Pathology of Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China.
  • Shen DD; Liangzhu Laboratory, Zhejiang University Medical Center, 1369 West Wenyi Road, Hangzhou 311121, China.
  • Tao X; Key Laboratory Experimental Teratology of the Ministry of Education and Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Cheeloo college of Medicine, Shandong University, Jinan, Shandong 250012, China.
  • Zhang H; Key Laboratory Experimental Teratology of the Ministry of Education and Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Cheeloo college of Medicine, Shandong University, Jinan, Shandong 250012, China.
  • Yan X; Department of Biophysics and Department of Pathology of Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China.
  • Zhao RJ; Liangzhu Laboratory, Zhejiang University Medical Center, 1369 West Wenyi Road, Hangzhou 311121, China.
  • He J; Key Laboratory Experimental Teratology of the Ministry of Education and Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Cheeloo college of Medicine, Shandong University, Jinan, Shandong 250012, China.
  • Guan Y; Department of Biophysics and Department of Pathology of Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China.
  • Zhang C; Liangzhu Laboratory, Zhejiang University Medical Center, 1369 West Wenyi Road, Hangzhou 311121, China.
  • Hou G; Key Laboratory Experimental Teratology of the Ministry of Education and Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Cheeloo college of Medicine, Shandong University, Jinan, Shandong 250012, China.
  • Zhang PJ; Key Laboratory Experimental Teratology of the Ministry of Education and Department of Physiology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, China.
  • Hou G; Key Laboratory Experimental Teratology of the Ministry of Education and Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Cheeloo college of Medicine, Shandong University, Jinan, Shandong 250012, China.
  • Li Z; Key Laboratory Experimental Teratology of the Ministry of Education and Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Cheeloo college of Medicine, Shandong University, Jinan, Shandong 250012, China.
  • Yu X; Key Laboratory Experimental Teratology of the Ministry of Education and Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Cheeloo college of Medicine, Shandong University, Jinan, Shandong 250012, China.
  • Chai RJ; Biomedical Isotope Research Center, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, China.
  • Guan YF; Biomedical Isotope Research Center, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, China.
  • Sun JP; Key Laboratory Experimental Teratology of the Ministry of Education and Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Cheeloo college of Medicine, Shandong University, Jinan, Shandong 250012, China.
  • Zhang Y; School of Pharmacy, Binzhou Medical University, Yantai, Shandong 264003, China.
Sci Adv ; 7(14)2021 04.
Article en En | MEDLINE | ID: mdl-33811074
Selective modulation of the heterotrimeric G protein α S subunit-coupled prostaglandin E2 (PGE2) receptor EP2 subtype is a promising therapeutic strategy for osteoporosis, ocular hypertension, neurodegenerative diseases, and cardiovascular disorders. Here, we report the cryo-electron microscopy structure of the EP2-Gs complex with its endogenous agonist PGE2 and two synthesized agonists, taprenepag and evatanepag (CP-533536). These structures revealed distinct features of EP2 within the EP receptor family in terms of its unconventional receptor activation and G protein coupling mechanisms, including activation in the absence of a typical W6.48 "toggle switch" and coupling to Gs via helix 8. Moreover, inspection of the agonist-bound EP2 structures uncovered key motifs governing ligand selectivity. Our study provides important knowledge for agonist recognition and activation mechanisms of EP2 and will facilitate the rational design of drugs targeting the PGE2 signaling system.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Sci Adv Año: 2021 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Sci Adv Año: 2021 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos