9NWP
Human delta 2 receptor activated by D-serine
Summary for 9NWP
| Entry DOI | 10.2210/pdb9nwp/pdb |
| EMDB information | 49889 |
| Descriptor | Glutamate receptor ionotropic, delta-2, D-SERINE (2 entities in total) |
| Functional Keywords | ligand-gated ion channel, ion channel, neurotransmitter receptor, transport protein |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 4 |
| Total formula weight | 377569.94 |
| Authors | Wang, H.,Ahmed, F.,Kumar Mondal, A.,Twomey, E.C. (deposition date: 2025-03-24, release date: 2025-09-24, Last modification date: 2025-12-10) |
| Primary citation | Wang, H.,Ahmed, F.,Khau, J.,Mondal, A.K.,Twomey, E.C. Delta-type glutamate receptors are ligand-gated ion channels. Nature, 647:1063-1071, 2025 Cited by PubMed Abstract: Delta-type ionotropic glutamate receptors (iGluRs), or GluDs, are members of the iGluR ligand-gated ion channel family, yet their function remains enigmatic. Although GluDs are widely expressed in the brain, play key roles in synaptic organization, and harbor disease-linked mutations, whether they retain iGluR-like channel function is debated as currents have not been directly observed. Here, we define GluDs as ligand-gated ion channels that are tightly regulated in cellular contexts by purifying human GluD2 (hGluD2) and directly characterizing its structure and function using cryo-electron microscopy (cryoEM) and bilayer recordings. We show that hGluD2 is activated by D-serine and γ-aminobutyric acid (GABA), with augmented activation at physiological temperatures. We reveal that hGluD2 contains an ion channel directly coupled to clamshell-like ligand-binding domains (LBDs), which are coordinated by the amino terminal domain (ATD) above the ion channel. Ligand binding triggers channel opening via an asymmetric mechanism, and a cerebellar ataxia point mutation in the LBD rearranges the receptor architecture and induces leak currents. Our findings demonstrate that GluDs possess the intrinsic biophysical properties of ligand-gated ion channels, reconciling prior conflicting observations to establish a framework for understanding their cellular regulation and for developing therapies targeting GluD2. PubMed: 40957579DOI: 10.1038/s41586-025-09610-x PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.69 Å) |
Structure validation
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