Fig. 3
From: AMPA receptor GluA2 subunit defects are a cause of neurodevelopmental disorders
Molecular modeling and predicted consequences of 6 GRIA2 de-novo missense variants Left panel: Six modeled GRIA2 de-novo missense variants (highlighted in purple within red rectangle) affecting the amino-terminal domain (ATD) and ligand-binding domain (LBD) of GluA2; Middle panel: particular of the wild-type GlUA2 residue; Right panel: particular of the mutated GluA2 residue. a For variant p.G47E, the presence of the glutamic acid residue (right panel) in place of the glycine residue (middle panel) is predicted to cause the formation of two hydrogen bonds with a neighboring arginine residue; hydrogen bond distances are shown for the mutant structure. b The presence of a Threonine residue in position 528 (right panel) is predicted to cause a slight change in the backbone conformation of the neighboring residues that, in turn, allows hydrogen bonding formation between the two chains forming the LBD domain. c Mutation p.F644L causes the loss of hydrophobic interactions between residue 644 and the side chain of Lys532. d For mutation p.T646N, the presence of a more hydrophilic Asparagine residue increases the distance between the distal chains by about 3 Å, at the interface of LBD and TMD (right panel). e For mutation p.V647L, increased hydrophobicity of Leucine (right panel) compared to Valine (middle panel) increases the separation of helices at the interface between LBD and TMD by about 2 Å. f For variant p.G792V, the presence of a more hydrophobic Valine residue in close proximity to the binding site is predicted to cause a sliding movement with respect to the neighboring chain, disrupting the interchain salt bridge between Glu655 and Lys797; hydrogen bond distance is shown in the wild-type GluA2 (middle panel)
