9B35

Ligand-binding and transmembrane domains of kainate receptor GluK2 in the open state, a complex with agonist glutamate and positive allosteric modulator BPAM344

9B35 の概要

• エントリーDOI: 10.2210/pdb9b35/pdb
• EMDBエントリー: 44128
• 分子名称: Glutamate receptor ionotropic, kainate 2, GLUTAMIC ACID (2 entities in total)
• 機能のキーワード: kainate receptor, gluk2, positive allosteric modulator, bpam344, open, glutamate, lbd-tmd, ligand-binding domain, transmembrane domain, membrane protein
• 由来する生物種: Rattus norvegicus (Norway rat)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 412494.86

構造登録者

Nadezhdin, K.D.,Gangwar, S.P.,Sobolevsky, A.I. (登録日: 2024-03-18, 公開日: 2024-05-22, 最終更新日: 2024-10-23)

主引用文献

Gangwar, S.P.,Yelshanskaya, M.V.,Nadezhdin, K.D.,Yen, L.Y.,Newton, T.P.,Aktolun, M.,Kurnikova, M.G.,Sobolevsky, A.I.
Kainate receptor channel opening and gating mechanism.
Nature, 630:762-768, 2024

PubMed Abstract: Kainate receptors, a subclass of ionotropic glutamate receptors, are tetrameric ligand-gated ion channels that mediate excitatory neurotransmission. Kainate receptors modulate neuronal circuits and synaptic plasticity during the development and function of the central nervous system and are implicated in various neurological and psychiatric diseases, including epilepsy, depression, schizophrenia, anxiety and autism. Although structures of kainate receptor domains and subunit assemblies are available, the mechanism of kainate receptor gating remains poorly understood. Here we present cryo-electron microscopy structures of the kainate receptor GluK2 in the presence of the agonist glutamate and the positive allosteric modulators lectin concanavalin A and BPAM344. Concanavalin A and BPAM344 inhibit kainate receptor desensitization and prolong activation by acting as a spacer between the amino-terminal and ligand-binding domains and a stabilizer of the ligand-binding domain dimer interface, respectively. Channel opening involves the kinking of all four pore-forming M3 helices. Our structures reveal the molecular basis of kainate receptor gating, which could guide the development of drugs for treatment of neurological disorders.

PubMed: 38778115
DOI: 10.1038/s41586-024-07475-0

実験手法

ELECTRON MICROSCOPY (3.4 Å)