Figure 5. Possible mechanism of positive allostery of DNRAbs on GluN2A-containing NMDARs.
(A) Individual domains within a GluN2A subunit. DWEYS is a mimetope of dsDNA and is the major binding site for DNRAbs. Model structure of 4TLM (Amin et al., 2017).
(B) Zn2+ acts as a negative allosteric modulator of GluN2A-containing NMDARs by inducing clam-shell closure of the ATD. The DWEYS motif is at the hinge of the ATD clam-shell and DNRAb binding may potentiate currents by forcing open the clam-shell.
Synaptic currents recorded from a CA1 pyramidal neuron with Schaffer collateral stimulation. Currents recorded at −70 mV in a solution containing no added Mg2+ (LPW, unpublished data).