8FQG
LBD conformation 1 (LBDconf1) of GluA2 flip Q isoform of AMPA receptor in complex with gain-of-function TARP gamma-2, with 150mM NaCl, 330uM CTZ, and 100mM glutamate (Open-Na260)
Summary for 8FQG
| Entry DOI | 10.2210/pdb8fqg/pdb |
| EMDB information | 29360 29387 |
| Descriptor | Glutamate receptor 2, GLUTAMIC ACID, CYCLOTHIAZIDE, ... (4 entities in total) |
| Functional Keywords | ionotropic glutamate receptor, ligand gated ion channel, ampa receptor, tarp gamma-2, transport protein |
| Biological source | Rattus norvegicus (Norway rat) |
| Total number of polymer chains | 4 |
| Total formula weight | 400385.87 |
| Authors | Nakagawa, T. (deposition date: 2023-01-06, release date: 2024-02-28, Last modification date: 2024-05-01) |
| Primary citation | Nakagawa, T.,Wang, X.T.,Miguez-Cabello, F.J.,Bowie, D. The open gate of the AMPA receptor forms a Ca 2+ binding site critical in regulating ion transport. Nat.Struct.Mol.Biol., 31:688-700, 2024 Cited by PubMed Abstract: Alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-propionic acid receptors (AMPARs) are cation-selective ion channels that mediate most fast excitatory neurotransmission in the brain. Although their gating mechanism has been studied extensively, understanding how cations traverse the pore has remained elusive. Here we investigated putative ion and water densities in the open pore of Ca-permeable AMPARs (rat GRIA2 flip-Q isoform) at 2.3-2.6 Å resolution. We show that the ion permeation pathway attains an extracellular Ca binding site (site-G) when the channel gate moves into the open configuration. Site-G is highly selective for Ca over Na, favoring the movement of Ca into the selectivity filter of the pore. Seizure-related N619K mutation, adjacent to site-G, promotes channel opening but attenuates Ca binding and thus diminishes Ca permeability. Our work identifies the importance of site-G, which coordinates with the Q/R site of the selectivity filter to ensure the preferential transport of Ca through the channel pore. PubMed: 38409505DOI: 10.1038/s41594-024-01228-3 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.01 Å) |
Structure validation
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