The N-terminal domains of both NR1 and NR2 subunits determine allosteric Zn2+ inhibition and glycine affinity of N-methyl-D-aspartate receptors.

Modulation of Triheteromeric NMDA Receptors by N-Terminal Domain Ligands

NMDA receptors (NMDARs) are heteromeric assemblies of NR1 and NR2(A-D) subunits with properties heavily influenced by the type of NR2 subunit incorporated. While NMDARs with only one type of NR2 subunit have been extensively characterized, little is known about receptors containing two different NR2 subunits, despite compelling evidence that such triheteromeric receptors exist in vivo. We used ...

The NR1 M3 domain mediates allosteric coupling in the N-methyl-D-aspartate receptor.

N-Methyl-D-aspartate (NMDA) receptors play a critical role in both development of the central nervous system and adult neuroplasticity. However, although the NMDA receptor presents a valuable therapeutic target, the relationship between its structure and functional properties has yet to be fully elucidated. To further explore the mechanism of receptor activation, we characterized two gain-of-fu...

The N - terminal domains of both NR 1 and NR 2 subunits determine allosteric Zn 2 + inhibition and glycine affinity of NMDA receptors

Identification and Mechanism of Action of Two Histidine Residues Underlying High-Affinity Zn2+ Inhibition of the NMDA Receptor

Zinc (Zn2+) inhibition of N-methyl-D-aspartate receptor (NMDAR) activity involves both voltage-independent and voltage-dependent components. Recombinant NR1/NR2A and NR1/NR2B receptors exhibit similar voltage-dependent block, but voltage-independent Zn2+ inhibition occurs with much higher affinity for NR1/NR2A than NR1/NR2B receptors (nanomolar versus micromolar IC50, respectively). Here, we sh...

New insights into the not-so-new NR3 subunits of N-methyl-D-aspartate receptor: localization, structure, and function.

The NR3 subunits (NR3A and NR3B) are new players in a well established field of N-methyl-d-aspartate (NMDA) receptors, previously involving the NR1 and NR2 subunits. Their incorporation into conventional NMDA receptors forms glutamate-activated NR1/NR2/NR3 triheteromers, whereas the omission of the glutamate-binding NR2 subunits results in excitatory glycine-activated NR1/NR3 diheteromers. Thes...