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 Gα_i and Gα_s 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).

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）。