Fig. 5: Conformational change of CRDs within the mGlu2-4 heterodimer during activation.
From: Structural basis of orientated asymmetry in a mGlu heterodimer
a Critical residues involved in the interaction between CRD and ECL2 in mGlu2 subunit (left) and mGlu4 subunit (right) in the mGlu2-4G complex. L-AP4 (left) and LY379268 (right) induced G protein activation in mGlu2C1-mGlu4C2 heterodimer (Ctr) without or with the indicated mutations in the CRD and ECL2 of mGlu2 subunit (b) or mGlu4 (c) subunit. Data are normalized by using the maximum response (Emax) of mGlu2-4 Ctr 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): (b), Ctr, E555A-K707A, Q558A-K707A, left: n = 3, 3, 3; right: n = 5, 5, 4; (c), Ctr, E568A-R738A, D563A-Q730A, left: n = 7, 5, 5; right: n = 8, 4, 5. The inserted graphs correspond to representative Emax and analyzed using one-way ANOVA with a Dunnett’s post-hoc multiple comparison test compared with Ctr to determine significance. ****P < 0.0001, ***P < 0.001, **P < 0.01, not significant (ns) >0.05. P values for (b): 0.0015, 0.0030, 0.0003, 0.0004; for (c), 0.0050, <0.0001, 0.0039, 0.8085 (from left to right). Source data are provided as a Source Data file.
