5JEI
Crystal structure of the GluA2 LBD in complex with FW
Summary for 5JEI
| Entry DOI | 10.2210/pdb5jei/pdb |
| Descriptor | Glutamate receptor 2,Glutamate receptor 2, SODIUM ION, 2-AMINO-3-(5-FLUORO-2,4-DIOXO-3,4-DIHYDRO-2H-PYRIMIDIN-1-YL)-PROPIONIC ACID, ... (11 entities in total) |
| Functional Keywords | transport protein, ligand binding domain, glutamate receptor 2 |
| Biological source | Rattus norvegicus (Rat) More |
| Cellular location | Cell membrane ; Multi-pass membrane protein : P19491 |
| Total number of polymer chains | 1 |
| Total formula weight | 31182.56 |
| Authors | Eibl, C.,Salazar, H.,Chebli, M.,Plested, A.J.R. (deposition date: 2016-04-18, release date: 2017-02-22, Last modification date: 2024-11-13) |
| Primary citation | Salazar, H.,Eibl, C.,Chebli, M.,Plested, A. Mechanism of partial agonism in AMPA-type glutamate receptors. Nat Commun, 8:14327-14327, 2017 Cited by PubMed Abstract: Neurotransmitters trigger synaptic currents by activating ligand-gated ion channel receptors. Whereas most neurotransmitters are efficacious agonists, molecules that activate receptors more weakly-partial agonists-also exist. Whether these partial agonists have weak activity because they stabilize less active forms, sustain active states for a lesser fraction of the time or both, remains an open question. Here we describe the crystal structure of an α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptor (AMPAR) ligand binding domain (LBD) tetramer in complex with the partial agonist 5-fluorowillardiine (FW). We validate this structure, and others of different geometry, using engineered intersubunit bridges. We establish an inverse relation between the efficacy of an agonist and its promiscuity to drive the LBD layer into different conformations. These results suggest that partial agonists of the AMPAR are weak activators of the receptor because they stabilize multiple non-conducting conformations, indicating that agonism is a function of both the space and time domains. PubMed: 28211453DOI: 10.1038/ncomms14327 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.229 Å) |
Structure validation
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