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  • 标题:An inactive receptor-G protein complex maintains the dynamic range of agonist-induced signaling
  • 本地全文:下载
  • 作者:Wonjo Jang ; C. Elizabeth Adams ; Heng Liu
  • 期刊名称:Proceedings of the National Academy of Sciences
  • 印刷版ISSN:0027-8424
  • 电子版ISSN:1091-6490
  • 出版年度:2020
  • 卷号:117
  • 期号:48
  • 页码:30755-30762
  • DOI:10.1073/pnas.2010801117
  • 出版社:The National Academy of Sciences of the United States of America
  • 摘要:Agonist binding promotes activation of G protein-coupled receptors (GPCRs) and association of active receptors with G protein heterotrimers. The resulting active-state ternary complex is the basis for conventional stimulus-response coupling. Although GPCRs can also associate with G proteins before agonist binding, the impact of such preassociated complexes on agonist-induced signaling is poorly understood. Here we show that preassociation of 5-HT 7 serotonin receptors with G s heterotrimers is necessary for agonist-induced signaling. 5-HT 7 receptors in their inactive state associate with G s , as these complexes are stabilized by inverse agonists and receptor mutations that favor the inactive state. Inactive-state 5-HT 7 –G s complexes dissociate in response to agonists, allowing the formation of conventional agonist–5-HT 7 –G s ternary complexes and subsequent G s activation. Inactive-state 5-HT 7 –G s complexes are required for the full dynamic range of agonist-induced signaling, as 5-HT 7 receptors spontaneously activate G s variants that cannot form inactive-state complexes. Therefore, agonist-induced signaling in this system involves two distinct receptor-G protein complexes, a conventional ternary complex that activates G proteins and an inverse-coupled binary complex that maintains the inactive state when agonist is not present.
  • 关键词:GPCR ; G protein ; ternary complex ; precoupling ; serotonin
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