Fig. 4: Agonist-bound structures of mGluR3 show common intersubunit interfaces that are re-shaped by allosteric modulators.

a Full length cryo-EM density map and protein model for LY379268 (agonist; LY37) and LY37/VU6023326 (agonist/PAM; LY37/VU602) bound mGluR3. b Full-length mGluR3 LY37/VU602 model with LY37 in purple and ions in black highlighting the inter LBD bottom lobe (LB2) distance measured from the Cα of E224 and inter-CRD distance measured from the Cα of C546. c Plot comparing inter-LB2 versus inter-CRD distance across reported agonist-bound homodimeric mGluR subtypes measured via conserved positions highlighted in (b). d mGluR3 LY37 (green) and mGluR3 LY37/VU602 (blue) structures aligned via the top lobe (LB1) of chain A. The angle between helix B and helix O and the angle between helix F of chain A and chain B is reported. Structural offsets are reported for residues T410 (2.7 Å), R206(1.8 Å), I530(2.2 Å), M547(3.9 Å), and E567 (5.2 Å). e Top and bottom views of single TMD alignments between LY37 and LY37/VU602 structures with offsets highlighted by red arrows. Alignments are performed for the entire TMD from residue 571 to the end of the model, including loops. f, g Side views comparing aligned TMDs for mGluR3 LY37 and mGluR3 LY37/VU602 structures. TM4 is hidden from the panel (g) for clarity. h Alignment of TMDs for mGluR3 LY37, mGluR3 LY37/VU602, mGluR2 agonist/PAM (7MTR), and mGluR2 agonist/PAM/G protein (7MTS). For clarity, TM4 is hidden from view. i Side views of LY37 and LY37/VU602 TMD dimer with TM6 shown in dark blue and the Cα of key residues highlighted. j Inter-TM6 interface profile measured by intersubunit Cα distance of outward facing residues for LY37 and LY37/VU602 structures. k Plot of inter TM6 distance across full-length homodimeric mGluR structures using two conserved positions.