Cryo-EM structure of human rhodopsin bound to an inhibitory G protein.
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.
Kang, Y; Kuybeda, O; de Waal, PW; Mukherjee, S; Van Eps, N; Dutka, P; Zhou, XE; Bartesaghi, A; Erramilli, S; Morizumi, T; Gu, X; Yin, Y; Liu, P; Jiang, Y; Meng, X; Zhao, G; Melcher, K; Ernst, OP; Kossiakoff, AA; Subramaniam, S; Xu, HE
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