9OOP
Human delta 2 receptor with R710W Cerebellar Ataxia mutation in the apo leak state
Summary for 9OOP
| Entry DOI | 10.2210/pdb9oop/pdb |
| EMDB information | 70668 |
| Descriptor | Human delta 2 receptor with R710W Cerebellar Ataxia mutation (1 entity in total) |
| Functional Keywords | ligand-gated ion channel, ion channel, neurotransmitter receptor, transport protein |
| Biological source | Homo sapiens |
| Total number of polymer chains | 4 |
| Total formula weight | 321452.12 |
| Authors | Wang, H.,Ahmed, F.,Khau, J.,Mondal, A.K.,Twomey, E.C. (deposition date: 2025-05-16, 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, also known as GluDs) are members of the iGluR ligand-gated ion channel family, yet their function remains unknown. Although GluDs are widely expressed in the brain, have key roles in synaptic organization, and harbour 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 and bilayer recordings. We show that hGluD2 is activated by D-serine and GABA (γ-aminobutyric acid), with augmented activation at physiological temperatures. We reveal that hGluD2 contains an ion channel directly coupled to clamshell-like ligand-binding domains, which are coordinated by the amino-terminal domain above the ion channel. Ligand binding triggers channel opening via an asymmetric mechanism, and a cerebellar ataxia point mutation in the ligand-binding domain 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 (3.73 Å) |
Structure validation
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