9P9F
Active substate 4 of the GluA4 homotetramer.
Summary for 9P9F
| Entry DOI | 10.2210/pdb9p9f/pdb |
| EMDB information | 71409 |
| Descriptor | Isoform 2 of Glutamate receptor 4, Voltage-dependent calcium channel gamma-2 subunit, GLUTAMIC ACID, ... (4 entities in total) |
| Functional Keywords | ampar, ion channel, glutamate receptor, ligand-gated, membrane protein |
| Biological source | Rattus norvegicus (Norway rat) More |
| Total number of polymer chains | 8 |
| Total formula weight | 474974.96 |
| Authors | Hale, W.D.,Huganir, R.L.,Twomey, E.C. (deposition date: 2025-06-24, release date: 2026-01-28, Last modification date: 2026-09-23) |
| Primary citation | Hale, W.D.,Wang, H.,Huganir, R.L.,Twomey, E.C. Structural basis for activation and conformational plasticity of the GluA4 AMPA receptor. Nat Commun, 17:-, 2026 Cited by PubMed Abstract: AMPA-subtype glutamate receptors (AMPARs) mediate excitatory synaptic transmission. AMPAR ion channels exhibit multiple subconductance states that tune neuronal responses to glutamate. GluA4 is the rarest subunit in the brain but is enriched in interneurons and the cerebellum. Rising evidence points to GluA4 AMPARs in the development of neurological diseases, but the structural mechanisms of GluA4 function remain enigmatic. Here, we show the distinct features of GluA4 that tune AMPAR function. We find that GluA4 AMPARs have a canonical "Y" shaped architecture where local dimer pairs are domain-swapped between the amino terminal domain (NTD) and ligand binding domain (LBD), both of which comprise the extracellular domain. All four LBDs are glutamate bound yet open the GluA4 ion channel by asymmetric hinging in all four channel helices. We observe that the glutamate-saturated LBD has conformational plasticity, which tunes the ion channel gate below. These data provide a framework for understanding channel subconductance, outline the distinct properties of GluA4, expand our understanding of conformational plasticity in AMPARs, and will inform therapeutic design. PubMed: 41656278DOI: 10.1038/s41467-026-68953-9 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.89 Å) |
Structure validation
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