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Structural basis and mechanism of activation of two different families of G proteins by the same GPCR
Nature Structural & Molecular Biology ( IF 12.5 ) Pub Date : 2021-11-10 , DOI: 10.1038/s41594-021-00679-2
Kamela O Alegre 1 , Navid Paknejad 2 , Minfei Su 1 , Jian-Shu Lou 1 , Jianyun Huang 1 , Kelsey D Jordan 3 , Edward T Eng 3 , Joel R Meyerson 1 , Richard K Hite 2 , Xin-Yun Huang 1
Affiliation  

The β1-adrenergic receptor (β1-AR) can activate two families of G proteins. When coupled to Gs, β1-AR increases cardiac output, and coupling to Gi leads to decreased responsiveness in myocardial infarction. By comparative structural analysis of turkey β1-AR complexed with either Gi or Gs, we investigate how a single G-protein-coupled receptor simultaneously signals through two G proteins. We find that, although the critical receptor-interacting C-terminal α5-helices on Gαi and Gαs interact similarly with β1-AR, the overall interacting modes between β1-AR and G proteins vary substantially. Functional studies reveal the importance of the differing interactions and provide evidence that the activation efficacy of G proteins by β1-AR is determined by the entire three-dimensional interaction surface, including intracellular loops 2 and 4 (ICL2 and ICL4).



中文翻译:

同一GPCR激活两个不同家族G蛋白的结构基础和机制

β 1 -肾上腺素能受体 (β 1 -AR) 可以激活两个 G 蛋白家族。当与 Gs 偶联时,β 1 -AR 会增加心输出量,而与 Gi 偶联会导致心肌梗死的反应性降低。通过对与 Gi 或 Gs 复合的火鸡 β 1 -AR的比较结构分析,我们研究了单个 G 蛋白偶联受体如何同时通过两种 G 蛋白发出信号。我们发现,尽管 Gα i和 Gα s上与受体相互作用的关键受体 C 末端 α5-螺旋与 β 1 -AR 的相互作用相似,但 β 1之间的整体相互作用模式-AR 和 G 蛋白差异很大。功能研究揭示了不同相互作用的重要性,并提供证据表明 β 1 -AR 对 G 蛋白的激活功效由整个三维相互作用表面决定,包括细胞内环 2 和 4(ICL2 和 ICL4)。

更新日期:2021-11-10
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