Structure of the intact NMDA receptors. (A) Structure of the glycine- and glutamate-bound GluN1-1b/2B NMDA receptor without CTDs (Protein Data Bank accession no. 5FXI; Tajima et al., 2016). (B) The GluN1 (1) and GluN2 (2) subunits are arranged as a dimer of heterodimers at the ATD and ABD layers in a 1-2-1-2 fashion. Note that the heterodimer pairs are interchanged between the ATD and ABD layers (i.e., subunit crossover). In the TMD layer, the GluN1 and GluN2 subunits are arranged as a tetramer with pseudo-fourfold symmetry. (C) Comparison of the two major conformational states observed in the presence of glycine and glutamate by cryo-EM/single-particle analysis. Shown in spheres are the Cα of the gating ring residues, GluN1-1b Arg684 and GluN2B Glu658, which are adjacent to the pore-forming M3 transmembrane helices. In the nonactive (Protein Data Bank accession no. 5FXI; Tajima et al., 2016) and active (Protein Data Bank accession no. 5FXG; Tajima et al., 2016) conformations, the distances between the two GluN2B Glu658 Cα atoms are ∼29 Å and ∼45 Å, respectively, indicating that degrees of tension in the ABD–TMD loops are different.