8FQE

LBD conformation 2 (LBDconf2) of GluA2 flip Q isoform of AMPA receptor in complex with gain-of-function TARP gamma2, with 10mM CaCl2, 140mM NMDG, 330uM CTZ, and 100mM L-glutamate (Open-Ca10)

Summary for 8FQE

• Entry DOI: 10.2210/pdb8fqe/pdb
• EMDB information: 29382 29385
• Descriptor: Glutamate receptor 2, GLUTAMIC ACID, CYCLOTHIAZIDE, ... (4 entities in total)
• Functional Keywords: inotropic glutamate receptors, ampa receptors, ligand gated ion channel, auxiliary subunit, tarp, stargazin, tarp gamma2, glutamate, calcium, neurotransmitter receptor, synaptic transmission, transport protein
• Biological source: Rattus norvegicus (Norway rat)
• Total number of polymer chains: 4
• Total formula weight: 397567.44

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

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: 38409505
DOI: 10.1038/s41594-024-01228-3

Experimental method

ELECTRON MICROSCOPY (3.14 Å)