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Structural basis of Gs and Gi recognition by the human glucagon receptor.
Qiao, Anna; Han, Shuo; Li, Xinmei; Li, Zhixin; Zhao, Peishen; Dai, Antao; Chang, Rulve; Tai, Linhua; Tan, Qiuxiang; Chu, Xiaojing; Ma, Limin; Thorsen, Thor Seneca; Reedtz-Runge, Steffen; Yang, Dehua; Wang, Ming-Wei; Sexton, Patrick M; Wootten, Denise; Sun, Fei; Zhao, Qiang; Wu, Beili.
Afiliación
  • Qiao A; CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
  • Han S; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
  • Li X; University of Chinese Academy of Sciences, Beijing 100049, China.
  • Li Z; CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
  • Zhao P; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
  • Dai A; University of Chinese Academy of Sciences, Beijing 100049, China.
  • Chang R; National Laboratory of Biomacromolecules, National Center of Protein Science-Beijing, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
  • Tai L; School of Pharmacy, Fudan University, Shanghai 201203, China.
  • Tan Q; Drug Discovery Biology and Department of Pharmacology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052, Australia.
  • Chu X; CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
  • Ma L; National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
  • Thorsen TS; School of Pharmacy, Fudan University, Shanghai 201203, China.
  • Reedtz-Runge S; University of Chinese Academy of Sciences, Beijing 100049, China.
  • Yang D; National Laboratory of Biomacromolecules, National Center of Protein Science-Beijing, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
  • Wang MW; CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
  • Sexton PM; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
  • Wootten D; CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
  • Sun F; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
  • Zhao Q; CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
  • Wu B; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Science ; 367(6484): 1346-1352, 2020 03 20.
Article en En | MEDLINE | ID: mdl-32193322
Class B G protein-coupled receptors, an important class of therapeutic targets, signal mainly through the Gs class of heterotrimeric G proteins, although they do display some promiscuity in G protein binding. Using cryo-electron microscopy, we determined the structures of the human glucagon receptor (GCGR) bound to glucagon and distinct classes of heterotrimeric G proteins, Gs or Gi1 These two structures adopt a similar open binding cavity to accommodate Gs and Gi1 The Gs binding selectivity of GCGR is explained by a larger interaction interface, but there are specific interactions that affect Gi more than Gs binding. Conformational differences in the receptor intracellular loops were found to be key selectivity determinants. These distinctions in transducer engagement were supported by mutagenesis and functional studies.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Glucagón / Receptores de Glucagón / Subunidades alfa de la Proteína de Unión al GTP Gi-Go / Subunidades alfa de la Proteína de Unión al GTP Gs Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Science Año: 2020 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Glucagón / Receptores de Glucagón / Subunidades alfa de la Proteína de Unión al GTP Gi-Go / Subunidades alfa de la Proteína de Unión al GTP Gs Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Science Año: 2020 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos