8fq3

LBD conformation 2 (LBDconf2) of GluA2 flip Q isoform N619K mutant of AMPA receptor in complex with gain-of-function TARP gamma-2, with 10mM CaCl2, 150mM NaCl, 1mM MgCl2, 330uM CTZ, and 100mM glutamate (Open-CaNaMg/N619K)

spinqualitylabelsall models 8fq3, resolution 3.17Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8fq3 is a 4 chain structure with sequence from Rattus norvegicus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.17Å Ligands: CYZ, GLU Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed 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(2+)-permeable AMPARs (rat GRIA2 flip-Q isoform) at 2.3-2.6 A resolution. We show that the ion permeation pathway attains an extracellular Ca(2+) binding site (site-G) when the channel gate moves into the open configuration. Site-G is highly selective for Ca(2+) over Na(+), favoring the movement of Ca(2+) into the selectivity filter of the pore. Seizure-related N619K mutation, adjacent to site-G, promotes channel opening but attenuates Ca(2+) binding and thus diminishes Ca(2+) 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(2+) through the channel pore. The open gate of the AMPA receptor forms a Ca(2+) binding site critical in regulating ion transport.,Nakagawa T, Wang XT, Miguez-Cabello FJ, Bowie D Nat Struct Mol Biol. 2024 Apr;31(4):688-700. doi: 10.1038/s41594-024-01228-3. , Epub 2024 Feb 26. PMID:38409505 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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