Functional analysis of DN-G proteins. (a) Time-course
for ligand-induced
changes in BRET of WT-Gαs or DN-Gαs (nanoLuc tagged) and
Gγ (Venus) at increasing concentrations of salmon calcitonin
(sCT) (arrow, A) followed by the addition of 30 μM GTP (arrow,
B) on membranes from HEK293 cells that lack endogenous Gαs and
were stably transfected with the human CTR; the rate and magnitude
of agonist-induced structural rearrangement are similar, but the DN-Gαs
is resistant to GTP-induced conformational rearrangement. (b) Comparison
of time-courses for agonist-induced changes in BRET of WT-Gαs/Gγ
and DN-Gαs/Gγ are shown for GLP-1(7–36)NH2 activated GLP-1R; both WT- and DN-Gαs report the same difference
in rate and extent of ligand-induced G protein conformational change
(A); however, after the addition of 30 μM GTP (B), the DN-Gαs
is less susceptible to conformational change. (c) time-course for
GLP-1(7–36)NH2-induced changes in BRET of WT-Gαi2 or DN-Gαi2 (nanoLuc tagged) and Gγ
(Venus) (A), followed by the addition of 30 μM GTP (B), on membranes
from HEK293 cells that lack endogenous Gαs/Gαq/11/Gα12/13
and were stably transfected with the human GLP-1 receptor. The rate
and magnitude of structural rearrangement are similar but the DN-Gαi2 is resistant to GTP-induced conformational rearrangement.
All data are N = 3 + SEM.