G-protein-coupled receptors comprise the largest family of mammalian transmembrane receptors. They mediate numerous cellular pathways by coupling with downstream signalling transducers, including the hetrotrimeric G proteins Gs (stimulatory) and Gi (inhibitory) and several arrestin proteins. The structural mechanisms that define how G-protein-coupled receptors selectively couple to a specific type of G protein or arrestin remain unknown. Here, using cryo-electron microscopy, we show that the major interactions between activated rhodopsin and Gi are mediated by the C-terminal helix of the Gi α-subunit, which is wedged into the cytoplasmic cavity of the transmembrane helix bundle and directly contacts the amino terminus of helix 8 of rhodopsin. Structural comparisons of inactive, Gi-bound and arrestin-bound forms of rhodopsin with inactive and Gs-bound forms of the β2-adrenergic receptor provide a foundation to understand the unique structural signatures that are associated with the recognition of Gs, Gi and arrestin by activated G-protein-coupled receptors.The cryo-electron microscopy structure of human rhodopsin bound to the inhibitory Gi protein-coupled receptor provides insights into ligand–receptor–G-protein interactions.

中文翻译：

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与抑制性 G 蛋白结合的人视紫质的冷冻电镜结构

G 蛋白偶联受体包括最大的哺乳动物跨膜受体家族。它们通过与下游信号转导因子耦合来介导许多细胞通路，包括异源三聚体 G 蛋白 Gs（刺激性）和 Gi（抑制性）以及几种抑制蛋白。定义 G 蛋白偶联受体如何选择性偶联特定类型的 G 蛋白或抑制蛋白的结构机制仍然未知。在这里，使用冷冻电子显微镜，我们表明活化视紫红质和 Gi 之间的主要相互作用是由 Gi α-亚基的 C 端螺旋介导的，它被楔入跨膜螺旋束的细胞质腔中并直接接触视紫质螺旋 8 的氨基末端。不活动的结构比较，