Extended Data Fig. 4: Modelling His208 as a key GluA2 NTD BD interface residue.

a, Structure of the GluA2 (red) and GluA1 (blue) hetero-tetrameric NTD by AlphaFold2-multimer predicts the favored occupation of GluA2 at the BD sites. Overlayed to the full-length AMPAR GluA1/GluA2 LBD and TMD (PDB 7oca). b, Structure of H208A mutated GluA2/A1 NTD by AlphaFold2-multimer predicts a breakage of the GluA2 BD interface (top), recapitulating the GluA1 homomer (bottom). c, Structure of the GluA2 (red) and GluA1 (blue) NTD by AlphaFold2-multimer accurately predicts key contacting residues (shown in grey) at the GluA2 BD interface. AlphaFold predictions with single point mutations at key interface forming residues cause a complete disruption of the BD interface compared to WT models (GluA2) and previously published structures (PDB: 7oca). d, Double point missense mutations (DPM) at respective GluA2 BD chains at His208 are modelled to destabilize the NTD tier, calculated as the ΔGstability of the structure. e–f, Single (SPM) and double point missense mutations (DPM) at respective GluA2 BD chains at His208 are modelled to reduce the binding affinity between interface contacts in the NTD tier, calculated as the ΔGbinding affinity of the structure.