9B33
Structure of concanavalin A (ConA) dimer from the open-state structure of kainate receptor GluK2 in complex with agonist glutamate and positive allosteric modulator BPAM344 bound to one ConA dimer. Type II interface between GluK2 ligand-binding domain and ConA
Summary for 9B33
| Entry DOI | 10.2210/pdb9b33/pdb |
| EMDB information | 44124 |
| Descriptor | Concanavalin V, ZINC ION, CALCIUM ION (3 entities in total) |
| Functional Keywords | kainate receptor, gluk2, positive allosteric modulator, bpam344, open, concanavalin a, cona, glutamate, membrane protein |
| Biological source | Canavalia ensiformis (jack bean) |
| Total number of polymer chains | 2 |
| Total formula weight | 51455.74 |
| Authors | Nadezhdin, K.D.,Gangwar, S.P.,Sobolevsky, A.I. (deposition date: 2024-03-18, release date: 2024-05-22, Last modification date: 2024-06-26) |
| Primary citation | Gangwar, S.P.,Yelshanskaya, M.V.,Nadezhdin, K.D.,Yen, L.Y.,Newton, T.P.,Aktolun, M.,Kurnikova, M.G.,Sobolevsky, A.I. Kainate receptor channel opening and gating mechanism. Nature, 630:762-768, 2024 Cited by PubMed Abstract: Kainate receptors, a subclass of ionotropic glutamate receptors, are tetrameric ligand-gated ion channels that mediate excitatory neurotransmission. Kainate receptors modulate neuronal circuits and synaptic plasticity during the development and function of the central nervous system and are implicated in various neurological and psychiatric diseases, including epilepsy, depression, schizophrenia, anxiety and autism. Although structures of kainate receptor domains and subunit assemblies are available, the mechanism of kainate receptor gating remains poorly understood. Here we present cryo-electron microscopy structures of the kainate receptor GluK2 in the presence of the agonist glutamate and the positive allosteric modulators lectin concanavalin A and BPAM344. Concanavalin A and BPAM344 inhibit kainate receptor desensitization and prolong activation by acting as a spacer between the amino-terminal and ligand-binding domains and a stabilizer of the ligand-binding domain dimer interface, respectively. Channel opening involves the kinking of all four pore-forming M3 helices. Our structures reveal the molecular basis of kainate receptor gating, which could guide the development of drugs for treatment of neurological disorders. PubMed: 38778115DOI: 10.1038/s41586-024-07475-0 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (4.07 Å) |
Structure validation
Download full validation report
