6FQI

GluA2(flop) G724C ligand binding core dimer bound to L-Glutamate (Form B) at 2.91 Angstrom resolution

6FQI の概要

• エントリーDOI: 10.2210/pdb6fqi/pdb
• 分子名称: Glutamate receptor 2, GLUTAMIC ACID (2 entities in total)
• 機能のキーワード: ampar receptor, ligand binding domain, glutamate, cross-linked dimer, membrane protein
• 由来する生物種: Rattus norvegicus (Norway rat); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 58943.91

構造登録者

Coombs, I.D.,Soto, D.,Gold, M.G.,Farrant, M.F.,Cull-Candy, S.G. (登録日: 2018-02-14, 公開日: 2019-03-13, 最終更新日: 2024-11-13)

主引用文献

Coombs, I.D.,Soto, D.,McGee, T.P.,Gold, M.G.,Farrant, M.,Cull-Candy, S.G.
Homomeric GluA2(R) AMPA receptors can conduct when desensitized.
Nat Commun, 10:4312-4312, 2019

PubMed Abstract: Desensitization is a canonical property of ligand-gated ion channels, causing progressive current decline in the continued presence of agonist. AMPA-type glutamate receptors (AMPARs), which mediate fast excitatory signaling throughout the brain, exhibit profound desensitization. Recent cryo-EM studies of AMPAR assemblies show their ion channels to be closed in the desensitized state. Here we present evidence that homomeric Q/R-edited AMPARs still allow ions to flow when the receptors are desensitized. GluA2(R) expressed alone, or with auxiliary subunits (γ-2, γ-8 or GSG1L), generates large fractional steady-state currents and anomalous current-variance relationships. Our results from fluctuation analysis, single-channel recording, and kinetic modeling, suggest that the steady-state current is mediated predominantly by conducting desensitized receptors. When combined with crystallography this unique functional readout of a hitherto silent state enabled us to examine cross-linked cysteine mutants to probe the conformation of the desensitized ligand binding domain of functioning AMPAR complexes.

PubMed: 31541113
DOI: 10.1038/s41467-019-12280-9

実験手法

X-RAY DIFFRACTION (2.91001156656 Å)