Postsynaptic density protein 95 – NMDA receptor subunit 2B protein-protein interaction (PSD-95/NR2B PPI)

The **PSD-95/NR2B protein-protein interaction** refers to the direct molecular association between **postsynaptic density protein 95 (PSD-95, also known as DLG4 or SAP90)** and the **NR2B subunit (now called GluN2B) of the N-methyl-D-aspartate (NMDA) receptor**. PSD-95 is a major scaffolding protein located in the postsynaptic density of excitatory synapses, where it anchors and clusters NMDA and AMPA-type glutamate receptors, organizes signaling complexes, and modulates synaptic function and plasticity. The second PDZ domain of PSD-95 binds to a specific C-terminal motif on the NR2B subunit, regulating the surface expression, localization, and gating properties of NMDA receptors[2][3][8]. This interaction is crucial for synaptic transmission, plasticity, and the molecular architecture of excitatory synapses[1][5]. Disruption of this interaction has therapeutic potential in conditions linked to excitotoxicity or abnormal synaptic signaling, such as stroke, neuropathic pain, and certain neurodegenerative or psychiatric diseases, and is the target of experimental drugs like Tat-NR2B9c[2][4][6].

Other names

PSD-95–NMDA receptor interactionDiscs large homolog 4–NMDA receptor subunit 2B interactionSAP90–GluN2B interaction

Disruption of the PSD-95/NR2B interaction to prevent downstream excitotoxic signaling or aberrant synaptic plasticity Inhibition of postsynaptic signaling complexes that promote excitotoxicity mediated by excessive NMDA receptor activity