EMDB/PDB/SASBDBから引用されている文献のデータベース

キーワード
構造解析手法	All X線回折 NMR 電子顕微鏡小角散乱中性子線回折線維回折粉末回折赤外分光 EPR FRET 理論モデルハイブリッド
著者・登録者
ジャーナル
IF	>30 >20 >10 >5 all

タイトル	Proton-triggered rearrangement of the AMPA receptor N-terminal domains impacts receptor kinetics and synaptic localization.
ジャーナル・号・ページ	Nat Struct Mol Biol, Year 2024
掲載日	2024年8月13日
著者	Josip Ivica / Nejc Kejzar / Hinze Ho / Imogen Stockwell / Viktor Kuchtiak / Alexander M Scrutton / Terunaga Nakagawa / Ingo H Greger /
PubMed 要旨	AMPA glutamate receptors (AMPARs) are ion channel tetramers that mediate the majority of fast excitatory synaptic transmission. They are composed of four subunits (GluA1-GluA4); the GluA2 subunit ...AMPA glutamate receptors (AMPARs) are ion channel tetramers that mediate the majority of fast excitatory synaptic transmission. They are composed of four subunits (GluA1-GluA4); the GluA2 subunit dominates AMPAR function throughout the forebrain. Its extracellular N-terminal domain (NTD) determines receptor localization at the synapse, ensuring reliable synaptic transmission and plasticity. This synaptic anchoring function requires a compact NTD tier, stabilized by a GluA2-specific NTD interface. Here we show that low pH conditions, which accompany synaptic activity, rupture this interface. All-atom molecular dynamics simulations reveal that protonation of an interfacial histidine residue (H208) centrally contributes to NTD rearrangement. Moreover, in stark contrast to their canonical compact arrangement at neutral pH, GluA2 cryo-electron microscopy structures exhibit a wide spectrum of NTD conformations under acidic conditions. We show that the consequences of this pH-dependent conformational control are twofold: rupture of the NTD tier slows recovery from desensitized states and increases receptor mobility at mouse hippocampal synapses. Therefore, a proton-triggered NTD switch will shape both AMPAR location and kinetics, thereby impacting synaptic signal transmission.
リンク	Nat Struct Mol Biol / PubMed:39138332
手法	EM (単粒子)
解像度	2.57 - 3.69 Å
構造データ	44232 9b5z EMDB-44232, PDB-9b5z: GluA2 flip Q in complex with TARPgamma2 at pH8, consensus structure of LBD-TMD-TARPgamma2 手法: EM (単粒子) / 解像度: 2.71 Å 44233 9b60 EMDB-44233, PDB-9b60: GluA2 flip Q in complex with TARPgamma2 at pH8, consensus structure of TMD-TARPgamma2 手法: EM (単粒子) / 解像度: 2.57 Å 44234 9b61 EMDB-44234, PDB-9b61: GluA2 flip Q in complex with TARPgamma2 at pH5, consensus structure of LBD-TMD-TARPgamma2 手法: EM (単粒子) / 解像度: 2.81 Å 44244 9b63 EMDB-44244, PDB-9b63: GluA2 flip Q in complex with TARPgamma2 at pH5, consensus structure of TMD-TARPgamma2 手法: EM (単粒子) / 解像度: 2.76 Å 44245 9b64 EMDB-44245, PDB-9b64: GluA2 flip Q in complex with TARPgamma2 at pH5, class23, structure of LBD-TMD-TARPgamma2 手法: EM (単粒子) / 解像度: 3.56 Å 44248 9b67 EMDB-44248, PDB-9b67: GluA2 flip Q in complex with TARPgamma2 at pH8, class1, structure of LBD-TMD-TARPgamma2 手法: EM (単粒子) / 解像度: 3.39 Å 44249 9b68 EMDB-44249, PDB-9b68: GluA2 flip Q in complex with TARPgamma2 at pH8, class1, structure of NTD 手法: EM (単粒子) / 解像度: 3.6 Å 44250 9b69 EMDB-44250, PDB-9b69: GluA2 flip Q in complex with TARPgamma2 at pH8, class12, structure of NTD 手法: EM (単粒子) / 解像度: 3.69 Å 44251 9b6a EMDB-44251, PDB-9b6a: GluA2 flip Q in complex with TARPgamma2 at pH8, class12, structure of LBD-TMD-TARPgamma2 手法: EM (単粒子) / 解像度: 3.35 Å
化合物	ChemComp-NAG: 2-acetamido-2-deoxy-beta-D-glucopyranose / N-アセチル-β-D-グルコサミン
由来	mus musculus (ハツカネズミ) rattus norvegicus (ドブネズミ)
キーワード	TRANSPORT PROTEIN / AMPA receptor / ionotropic glutamate receptor / ion channel / auxiliary subunit