Fig. 6: Conformational change of 7TM within mGlu2-4 heterodimer during activation.

a Comparison of the conformational changes within mGlu4 7TM between mGlu4 subunit in mGlu2-4_G complex and mGlu4 subunit in mGlu2_G-4 complex (PDB: 8JD5). Left: Side view. Right: magnified view. b Comparison of the conformational changes within mGlu2 7TM between mGlu4 subunit in mGlu2-4_G complex and mGlu4 subunit in mGlu2_G-4 complex (PDB: 8JD5). Left: Side view. Right: magnified view. c, d Glu-induced G protein activation in mGlu2_C1-mGlu4_C2 heterodimer (Ctr), mGlu2-2 (WT) or mGlu4-4 homodimer (WT), without or with the indicated mutations in TM3, TM5 and TM6. Data are normalized by using the maximum response (E_max) of Ctr or indicated WT and present as mean ± s.e.m. from at least three independent biological replicates, each performed in triplicate. The indicated number of independent experiments (n): (c), left: Ctr, Y678^3.56A, I772^5.59A, Y792^6.44A, n = 11, 5, 3, 4; right: WT, Y678^3.56A, I772^5.59A, Y792^6.44A, n = 4, 4, 3, 4; (d), left: Ctr, A658^3.55Y, F747^5.59A, Y767^6.44A, n = 7, 4, 5, 4; right: WT, A658^3.55Y, F747^5.59A, Y767^6.44A, n = 9, 7, 4, 6. The inserted graphs correspond to representative E_max and analyzed using one-way ANOVA with a Dunnett’s post-hoc multiple comparison test compared with Ctr or WT to determine significance. ****P < 0.0001, ***P < 0.001, **P < 0.01, *P < 0.05, not significant (ns) >0.05. P values for (c): 0.0080, 0.5383, 0.0304, <0.0001, 0.9794, 0.0001; for (d), 0.9997, 0.2513, 0.9758, <0.0001, 0.0048, 0.0083 (from left to right). Source data are provided as a Source Data file.