Vance, K. M., Simorowski, N., Traynelis, S. F., Furukawa, H. (April 2011) Ligand-specific deactivation time course of GluN1/GluN2D NMDA receptors. Nature Communications, 2. ISSN 2041-1723 (Public Dataset)
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Abstract
N-methyl-D-aspartate (NMDA) receptors belong to the family of ionotropic glutamate receptors that mediate a majority of excitatory synaptic transmission. One unique property of GluN1/GluN2D NMDA receptors is an unusually prolonged deactivation time course following the removal of L-glutamate. Here we show, using x-ray crystallography and electrophysiology, that the deactivation time course of GluN1/GluN2D receptors is influenced by the conformational variability of the ligand-binding domain (LBD) as well as the structure of the activating ligand. L-glutamate and L-CCG-IV induce significantly slower deactivation time courses compared with other agonists. Crystal structures of the isolated GluN2D LBD in complex with various ligands reveal that the binding of L-glutamate induces a unique conformation at the backside of the ligand-binding site in proximity to the region at which the transmembrane domain would be located in the intact receptors. These data suggest that the activity of the GluN1/GluN2D NMDA receptor is controlled distinctively by the endogenous neurotransmitter L-glutamate.
| Item Type: | Paper |
|---|---|
| Additional Information: | |
| Uncontrolled Keywords: | d-aspartate receptors glutamate receptors crystal structures homocysteic acid binding core synaptic currents false transmitter channel kinetics central neurons partial agonism |
| Subjects: | bioinformatics > genomics and proteomics > small molecules > NMDA receptor |
| CSHL Authors: | |
| Communities: | CSHL labs > Furukawa lab |
| Depositing User: | Leigh Johnson |
| Date: | April 2011 |
| Date Deposited: | 06 Mar 2012 19:02 |
| Last Modified: | 10 Sep 2019 16:14 |
| PMCID: | PMC3302728 |
| Related URLs: | |
| Dataset ID: | |
| URI: | https://repository.cshl.edu/id/eprint/25156 |
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