2XXT

Crystal structure of the GluK2 (GluR6) wild-type LBD dimer in complex with kainate

2XXT の概要

• エントリーDOI: 10.2210/pdb2xxt/pdb
• 関連するPDBエントリー: 1S50 1S7Y 1S9T 1SD3 1TT1 1YAE 2I0B 2I0C 2XXR 2XXU 2XXV 2XXW 2XXX 2XXY
• 分子名称: GLUTAMATE RECEPTOR, IONOTROPIC KAINATE 2, 3-(CARBOXYMETHYL)-4-ISOPROPENYLPROLINE, SODIUM ION, ... (5 entities in total)
• 機能のキーワード: transport protein
• 由来する生物種: RATTUS NORVEGICUS (NORWAY RAT)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 59759.78

構造登録者

Nayeem, N.,Mayans, O.,Green, T. (登録日: 2010-11-12, 公開日: 2011-02-09, 最終更新日: 2023-12-20)

主引用文献

Nayeem, N.,Mayans, O.,Green, T.
Conformational Flexibility of the Ligand-Binding Domain Dimer in Kainate Receptor Gating and Desensitization
J.Neurosci., 31:2916-, 2011

PubMed Abstract: AMPA- and kainate (KA)-selective ionotropic glutamate receptors (iGluRs) respond to agonist by opening (gating), then closing (desensitizing) in quick succession. Gating has been linked to agonist-induced changes within the ligand-binding domain (LBD), and desensitization to rearrangement of a dimer formed by neighboring LBDs. To explore the role of dimer conformation in both gating and desensitization, we compared the conformational effects of two kainate receptor mutants. The first, GluK2-D776K, blocks desensitization of macroscopic current responses ("macroscopic desensitization"). The second, GluK2-M770K, accelerates macroscopic desensitization and eliminates the effects of external ions on channel kinetics. Using structures determined by x-ray crystallography, we found that in both mutants the introduced lysines act as tethered cations, displacing sodium ions from their binding sites within the dimer interface. This results in new inter- and intra-protomer contacts in D776K and M770K respectively, explaining the effects of these mutations on dimer stability and desensitization kinetics. Further, chloride binding was unaffected by the M770K mutation, even though binding of sodium ions has been proposed to promote dimer stability by stabilizing anion binding. This suggests sodium binding may affect receptor function more directly than currently supposed. Notably, we also observed a ligand-specific shift in dimer conformation when comparing LBD dimers in complex with glutamate or the partial agonist KA, revealing a previously unidentified role for dimer orientation in iGluR gating.

PubMed: 21414913
DOI: 10.1523/JNEUROSCI.4771-10.2011

実験手法

X-RAY DIFFRACTION (1.9 Å)