Extended Data Figure 7 |. A model for GABA_B signaling and desensitization.

a, Agonist binding to GABA_B1 receptor causes the dissociation of Gβγ heterodimer from Gα. Four copies of Gβγ bind to a GIRK channel tetramer, resulting in channel activation. Afterwards, KCTD bound to the GABA_B2 C-terminus strips four copies of Gβγ from the GIRK channel and deactivates it. Following nucleotide hydrolysis, GDP-bound Gα binds to Gβγ, sequestering it from KCTD and priming the system for another signaling cycle. b, Calculated energies for the series of progressively tighter binding events are commensurate with the approximate energy released by GTP hydrolysis.