Fig. 3: Genetically encoded tools for location-selective perturbation of GPCR signaling.

a, The peptide inhibitor GαCT disrupts GPCR signaling by binding to the Gα protein interaction surface on the GPCR, thereby preventing GPCR–Gα coupling. b, The peptide inhibitor GRKct interferes with Gβγ signaling by blocking the interaction between Gβγ and GRKs. c, The peptide inhibitor PKI binds to the catalytic subunit of PKA (PKAcat), effectively inhibiting PKA activity. d, A conformation-specific nanobody targeting the active state of the GPCR perturbs G protein recruitment. e, Endosome-selective perturbation of GPCR signaling is achieved by fusing the conformation-specific nanobody with an endosome-targeting motif, restricting its action to endosomal compartments. f, Inducible plasma-membrane-selective perturbation of GPCR signaling involves targeting FKBP to the plasma membrane and fusing FRB to the C-terminus of a GPCR conformation-specific nanobody. Upon rapamycin treatment, FKBP and FRB heterodimerize, leading to the translocation of the nanobody to the plasma membrane for location-specific perturbation of GPCR signaling.