Neurotransmitter ligands activate ionotropic glutamate receptor (iGluR) ion channels by binding to the ligand-binding domain (LBD), triggering channel opening. The conserved aspartate residue D732 plays a crucial role in controlling ligand potency and channel activity. Mutations at this position can lead to NMDA receptors that are solely activated by glutamate, bypassing the need for glycine. A homomeric iGluR from Trichoplax adhaerens has evolved into a leak channel due to native mutations at this residue, inhibited by neurotransmitter binding. The D732L and D732F substitutions in GluN1 subunits yield NMDA receptors activated solely by glutamate, with no dependence on glycine. These mutations render GluN1 subunits constitutively active, suggesting a dominant contribution of this residue to both ligand recognition and channel activity across different iGluRs.
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by Seljeset,S.,... at www.biorxiv.org 08-06-2023
https://www.biorxiv.org/content/10.1101/2023.08.03.551817v2Deeper Inquiries