Ionotropic glutamate-like receptor δ2 binds d -serine and glycine

• DOI: 10.1073/pnas.0703718104
• Publication Date: 2007-08-22T00:48:23Z
• Authors: Peter Naur; Kasper B. Hansen; Anders S. Kristensen; Shashank M. Dravid; Darryl S. Pickering; Lars Olsen; Bente Vestergaard; Jan Egebjerg; Michael Gajhede; Stephen F. Traynelis; Jette S. Kastrup
• Keywords: Ionotropic glutamate receptor; Homomeric

The orphan glutamate-like receptor GluRδ2 is predominantly expressed in Purkinje cells of the central nervous system. classification to ionotropic glutamate family based on sequence similarities, because does not form functional homomeric glutamate-gated ion channels transfected cells. Studies −/− knockout mice as well with naturally occurring mutations gene have demonstrated an essential role cerebellar long-term depression, motor learning, coordination, and synaptogenesis. However, lack a known agonist has hampered investigations function GluRδ2. In this study, ligand-binding core (GluRδ2–S1S2) was found bind neutral amino acids such d -serine glycine, by isothermal titration calorimetry. Direct evidence for binding structural rearrangements cleft GluRδ2–S1S2 provided x-ray structures its apo complex -serine. Functionally, glycine were shown inactivate spontaneous ion-channel conductance containing lurcher mutation (EC 50 values, 182 507 μM, respectively). These data demonstrate that capable ligands closure can induce conformational changes alter permeation.