3B7D

Crystal structure of the GLUR2 ligand binding core (HS1S2J) in complex with CNQX at 2.5 A resolution

3B7D の概要

• エントリーDOI: 10.2210/pdb3b7d/pdb
• 関連するPDBエントリー: 1FTJ 1FTL 1FTM 1FTO
• 分子名称: Glutamate receptor 2, 7-nitro-2,3-dioxo-2,3-dihydroquinoxaline-6-carbonitrile (3 entities in total)
• 機能のキーワード: s1s2, cnqx, structural genomics, psi-2, protein structure initiative, center for structures of membrane proteins, csmp, cell junction, glycoprotein, ion transport, ionic channel, lipoprotein, palmitate, phosphorylation, postsynaptic cell membrane, receptor, rna editing, synapse, transmembrane, transport, membrane protein
• 由来する生物種: Rattus norvegicus (Norway rat); 詳細
• 細胞内の位置: Cell membrane; Multi-pass membrane protein: P19491
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 234461.52

構造登録者

Hays, F.A.,Center for Structures of Membrane Proteins (CSMP) (登録日: 2007-10-30, 公開日: 2007-11-20, 最終更新日: 2024-11-20)

主引用文献

Menuz, K.,Stroud, R.M.,Nicoll, R.A.,Hays, F.A.
TARP auxiliary subunits switch AMPA receptor antagonists into partial agonists.
Science, 318:815-817, 2007

PubMed Abstract: Quinoxalinedione compounds such as 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) are the most commonly used alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonists. However, we find that in the presence of transmembrane AMPA receptor regulatory proteins (TARPs), which are AMPA receptor auxiliary subunits, CNQX acts as a partial agonist. CNQX induced small depolarizing currents in neurons of the central nervous system, and reconstitution of this agonist activity required coexpression of TARPs. A crystal structure of CNQX bound to the TARP-less AMPA receptor ligand-binding domain showed that, although CNQX induces partial domain closure, this movement is not transduced into linker separation, suggesting that TARPs may increase agonist efficacy by strengthening the coupling between domain closure and channel opening. Our results demonstrate that the presence of an auxiliary subunit can determine whether a compound functions as an agonist or antagonist.

PubMed: 17975069
DOI: 10.1126/science.1146317

実験手法

X-RAY DIFFRACTION (2.5 Å)