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. Author manuscript; available in PMC: 2022 Dec 13.
Published in final edited form as: Cell. 2022 Sep 27;185(21):3950–3965.e25. doi: 10.1016/j.cell.2022.09.019

Figure 2. Gαs active-state inhibitor GN13 inhibits Gαs-mediated adenylyl cyclase activation.

Figure 2.

(A) Illustration of active-state binders inhibiting Gαs-mediated AC activation.

(B) Active-state binders inhibited PPI between Gαs/GNP and AC. Mean ± SD, n = 3.

(C) Gαs/GNP-mediated AC activation was inhibited by active-state binders. Mean ± SE, n = 3.

(D) Structure of the resynthesized cyclic peptide GN13.

(E) Illustration of GN13 inhibiting GPCR-stimulated Gαs/AC activity in cells.

(F) GN13 inhibited ISO-stimulated cAMP production in HEK293 cell membranes. Mean ± SD, n = 3.

(G) Design of a cell-permeable GN13 analog, cpGN13.

(H) Pretreatment with cpGN13 for 10 min inhibited ISO-stimulated cAMP production in live HEK293 cells. Mean ± SD, n = 3. Two-tailed unpaired t tests (data after 5 min).

See also Figure S2.