9N4P

Composite map for GluK2-1xNeto2 in the apo state

9N4P の概要

• エントリーDOI: 10.2210/pdb9n4p/pdb
• EMDBエントリー: 48901
• 分子名称: Glutamate receptor ionotropic, kainate 2, Neuropilin and tolloid-like protein 2, alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (7 entities in total)
• 機能のキーワード: kainate receptor, gluk2, ion channel, neto2, 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: 5
• 化学式量合計: 493922.82

構造登録者

Gangwar, S.P.,Yelshanskaya, M.V.,Yen, L.Y.,Newton, T.P.,Sobolevsky, A.I. (登録日: 2025-02-03, 公開日: 2025-09-17, 最終更新日: 2025-11-26)

主引用文献

Gangwar, S.P.,Yelshanskaya, M.V.,Yen, L.Y.,Newton, T.P.,Sobolevsky, A.I.
Activation of kainate receptor GluK2-Neto2 complex.
Nat.Struct.Mol.Biol., 32:2176-2184, 2025

PubMed Abstract: Kainate receptors (KARs) are tetrameric, ligand-gated ion channels of the ionotropic glutamate receptor family that mediate excitatory neurotransmission and modulate neuronal circuits and synaptic plasticity during development of the central nervous system. KARs are implicated in psychiatric and neurological diseases and represent a target of therapeutic intervention. Native KARs form complexes with neuropilin and tolloid-like auxiliary subunits (Neto1 and Neto2), which modulate their function, trafficking and synaptic localization. Here we present structures of rat GluK2 KAR in the apo closed state and in the open states activated by agonist kainate and positive allosteric modulator BPAM344, solved in the presence and absence of Neto2 using time-resolved cryo-electron microscopy. While the binding of Neto2 does not change the behavior of individual or dimeric ligand-binding domains (LBDs) or the ion channel, it prevents tightening of the interface between two LBD dimers during activation and slows the kinetics of deactivation. Our structures illuminate the mechanism of KAR activation and its modulation by Neto2.

PubMed: 40846810
DOI: 10.1038/s41594-025-01656-9

実験手法

ELECTRON MICROSCOPY (3.58 Å)