5JEI

Crystal structure of the GluA2 LBD in complex with FW

5JEI の概要

• エントリーDOI: 10.2210/pdb5jei/pdb
• 分子名称: Glutamate receptor 2,Glutamate receptor 2, SODIUM ION, 2-AMINO-3-(5-FLUORO-2,4-DIOXO-3,4-DIHYDRO-2H-PYRIMIDIN-1-YL)-PROPIONIC ACID, ... (11 entities in total)
• 機能のキーワード: transport protein, ligand binding domain, glutamate receptor 2
• 由来する生物種: Rattus norvegicus (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: 1
• 化学式量合計: 31182.56

構造登録者

Eibl, C.,Salazar, H.,Chebli, M.,Plested, A.J.R. (登録日: 2016-04-18, 公開日: 2017-02-22, 最終更新日: 2024-11-13)

主引用文献

Salazar, H.,Eibl, C.,Chebli, M.,Plested, A.
Mechanism of partial agonism in AMPA-type glutamate receptors.
Nat Commun, 8:14327-14327, 2017

PubMed Abstract: Neurotransmitters trigger synaptic currents by activating ligand-gated ion channel receptors. Whereas most neurotransmitters are efficacious agonists, molecules that activate receptors more weakly-partial agonists-also exist. Whether these partial agonists have weak activity because they stabilize less active forms, sustain active states for a lesser fraction of the time or both, remains an open question. Here we describe the crystal structure of an α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptor (AMPAR) ligand binding domain (LBD) tetramer in complex with the partial agonist 5-fluorowillardiine (FW). We validate this structure, and others of different geometry, using engineered intersubunit bridges. We establish an inverse relation between the efficacy of an agonist and its promiscuity to drive the LBD layer into different conformations. These results suggest that partial agonists of the AMPAR are weak activators of the receptor because they stabilize multiple non-conducting conformations, indicating that agonism is a function of both the space and time domains.

PubMed: 28211453
DOI: 10.1038/ncomms14327

実験手法

X-RAY DIFFRACTION (1.229 Å)