Fig. 3: Structural analysis of agonists-bound GluN1b-GluN2B NMDARs complexed to Fab2.
From: Development and characterization of functional antibodies targeting NMDA receptors
a–b Cryo-EM density of the non-active1 3D class at overall resolution of 3.92 Å from the ‘side’ (a) and ‘top’ (b) of the N-terminus. Densities for TMD, LBD, and ATD of GluN1b (magenta) and GluN2B (dark green) and Fab2 heavy chain (orange) and light chain (light pink) were observed. The structure was solved in the presence of 1 mM glycine and glutamate. c The molecular model built based on the cryo-EM density in the same color code as in panels a and b. d Zoomed view of the ATD-Fab2 interaction site demonstrating residues from CDR 1 and 3 of the heavy chain are mediating polar and hydrophobic interactions. e–f Interacting residues, Asp58, His60, and Arg67, were mutated to Ala (panel e) or Trp (panel f) and measured for inhibitory effects as in Fig. 1. The Ala triple mutant slightly retains the inhibitory effect whereas the Trp triple mutant completely removes the effect.
