+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 8usw | |||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
タイトル | CNQX-bound GluN1a-3A NMDA receptor | |||||||||||||||
要素 |
| |||||||||||||||
キーワード | MEMBRANE PROTEIN / Channel / receptor | |||||||||||||||
機能・相同性 | 機能・相同性情報 negative regulation of dendritic spine development / pons maturation / regulation of cell communication / positive regulation of Schwann cell migration / EPHB-mediated forward signaling / Assembly and cell surface presentation of NMDA receptors / olfactory learning / dendritic branch / conditioned taste aversion / regulation of respiratory gaseous exchange ...negative regulation of dendritic spine development / pons maturation / regulation of cell communication / positive regulation of Schwann cell migration / EPHB-mediated forward signaling / Assembly and cell surface presentation of NMDA receptors / olfactory learning / dendritic branch / conditioned taste aversion / regulation of respiratory gaseous exchange / protein localization to postsynaptic membrane / propylene metabolic process / response to glycine / glutamate receptor activity / regulation of monoatomic cation transmembrane transport / voltage-gated monoatomic cation channel activity / Assembly and cell surface presentation of NMDA receptors / Synaptic adhesion-like molecules / RAF/MAP kinase cascade / NMDA glutamate receptor activity / parallel fiber to Purkinje cell synapse / NMDA selective glutamate receptor complex / response to morphine / calcium ion transmembrane import into cytosol / glutamate binding / neuromuscular process / protein heterotetramerization / positive regulation of calcium ion transport into cytosol / positive regulation of reactive oxygen species biosynthetic process / regulation of synapse assembly / glycine binding / regulation of axonogenesis / regulation of dendrite morphogenesis / male mating behavior / suckling behavior / startle response / response to amine / dendrite development / regulation of neuronal synaptic plasticity / monoatomic cation transmembrane transport / associative learning / monoatomic cation transport / social behavior / excitatory synapse / ligand-gated monoatomic ion channel activity / positive regulation of excitatory postsynaptic potential / cellular response to glycine / positive regulation of dendritic spine maintenance / Unblocking of NMDA receptors, glutamate binding and activation / cellular response to manganese ion / phosphatase binding / glutamate receptor binding / long-term memory / regulation of neuron apoptotic process / monoatomic cation channel activity / prepulse inhibition / calcium ion homeostasis / synaptic cleft / glutamate-gated receptor activity / response to fungicide / glutamate-gated calcium ion channel activity / presynaptic active zone membrane / dendrite membrane / ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential / sensory perception of pain / presynaptic modulation of chemical synaptic transmission / response to amphetamine / ionotropic glutamate receptor signaling pathway / hippocampal mossy fiber to CA3 synapse / positive regulation of synaptic transmission, glutamatergic / adult locomotory behavior / regulation of membrane potential / excitatory postsynaptic potential / learning / protein phosphatase 2A binding / synaptic membrane / synaptic transmission, glutamatergic / transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential / postsynaptic density membrane / regulation of long-term neuronal synaptic plasticity / visual learning / modulation of chemical synaptic transmission / calcium channel activity / response to organic cyclic compound / regulation of synaptic plasticity / terminal bouton / cerebral cortex development / memory / intracellular calcium ion homeostasis / synaptic vesicle membrane / response to calcium ion / neuron cellular homeostasis / calcium ion transport / rhythmic process / synaptic vesicle / presynapse / signaling receptor activity / presynaptic membrane / amyloid-beta binding / protein-containing complex assembly 類似検索 - 分子機能 | |||||||||||||||
生物種 | Homo sapiens (ヒト) | |||||||||||||||
手法 | 電子顕微鏡法 / 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 4.23 Å | |||||||||||||||
データ登録者 | Michalski, K. / Furukawa, H. | |||||||||||||||
資金援助 | 米国, 4件
| |||||||||||||||
引用 | ジャーナル: Sci Adv / 年: 2024 タイトル: Structure and function of GluN1-3A NMDA receptor excitatory glycine receptor channel. 著者: Kevin Michalski / Hiro Furukawa / 要旨: -methyl-d-aspartate receptors (NMDARs) and other ionotropic glutamate receptors (iGluRs) mediate most of the excitatory signaling in the mammalian brains in response to the neurotransmitter glutamate. ...-methyl-d-aspartate receptors (NMDARs) and other ionotropic glutamate receptors (iGluRs) mediate most of the excitatory signaling in the mammalian brains in response to the neurotransmitter glutamate. Uniquely, NMDARs composed of GluN1 and GluN3 are activated exclusively by glycine, the neurotransmitter conventionally mediating inhibitory signaling when it binds to pentameric glycine receptors. The GluN1-3 NMDARs are vital for regulating neuronal excitability, circuit function, and specific behaviors, yet our understanding of their functional mechanism at the molecular level has remained limited. Here, we present cryo-electron microscopy structures of GluN1-3A NMDARs bound to an antagonist, CNQX, and an agonist, glycine. The structures show a 1-3-1-3 subunit heterotetrameric arrangement and an unprecedented pattern of GluN3A subunit orientation shift between the glycine-bound and CNQX-bound structures. Site-directed disruption of the unique subunit interface in the glycine-bound structure mitigated desensitization. Our study provides a foundation for understanding the distinct structural dynamics of GluN3 that are linked to the unique function of GluN1-3 NMDARs. | |||||||||||||||
履歴 |
|
-構造の表示
構造ビューア | 分子: MolmilJmol/JSmol |
---|
-ダウンロードとリンク
-ダウンロード
PDBx/mmCIF形式 | 8usw.cif.gz | 464.1 KB | 表示 | PDBx/mmCIF形式 |
---|---|---|---|---|
PDB形式 | pdb8usw.ent.gz | 342.5 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 8usw.json.gz | ツリー表示 | PDBx/mmJSON形式 | |
その他 | その他のダウンロード |
-検証レポート
文書・要旨 | 8usw_validation.pdf.gz | 1.3 MB | 表示 | wwPDB検証レポート |
---|---|---|---|---|
文書・詳細版 | 8usw_full_validation.pdf.gz | 1.4 MB | 表示 | |
XML形式データ | 8usw_validation.xml.gz | 82.8 KB | 表示 | |
CIF形式データ | 8usw_validation.cif.gz | 128.4 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/us/8usw ftp://data.pdbj.org/pub/pdb/validation_reports/us/8usw | HTTPS FTP |
-関連構造データ
関連構造データ | 42520MC 8usxC 8uueC M: このデータのモデリングに利用したマップデータ C: 同じ文献を引用 (文献) |
---|---|
類似構造データ | 類似検索 - 機能・相同性F&H 検索 |
-リンク
-集合体
登録構造単位 |
|
---|---|
1 |
|
-要素
#1: タンパク質 | 分子量: 95041.672 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: Grin1 発現宿主: Spodoptera frugiperda (ツマジロクサヨトウ) 参照: UniProt: P35439 #2: タンパク質 | 分子量: 104837.195 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: GRIN3A 発現宿主: Spodoptera frugiperda (ツマジロクサヨトウ) 参照: UniProt: Q8TCU5 #3: 化合物 | 分子量: 232.152 Da / 分子数: 2 / 由来タイプ: 合成 / 式: C9H4N4O4 / タイプ: SUBJECT OF INVESTIGATION 研究の焦点であるリガンドがあるか | Y | |
---|
-実験情報
-実験
実験 | 手法: 電子顕微鏡法 |
---|---|
EM実験 | 試料の集合状態: PARTICLE / 3次元再構成法: 単粒子再構成法 |
-試料調製
構成要素 | 名称: CNQX-bound GluN1-3A NMDA receptor / タイプ: COMPLEX / Entity ID: #1-#2 / 由来: RECOMBINANT |
---|---|
分子量 | 値: 0.4 MDa / 実験値: NO |
由来(天然) | 生物種: Homo sapiens (ヒト) |
由来(組換発現) | 生物種: Spodoptera frugiperda (ツマジロクサヨトウ) |
緩衝液 | pH: 7.5 |
試料 | 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES |
急速凍結 | 凍結剤: ETHANE |
-電子顕微鏡撮影
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |
---|---|
顕微鏡 | モデル: FEI TITAN KRIOS |
電子銃 | 電子線源: FIELD EMISSION GUN / 加速電圧: 300 kV / 照射モード: OTHER |
電子レンズ | モード: OTHER / 最大 デフォーカス(公称値): 2200 nm / 最小 デフォーカス(公称値): 800 nm / Cs: 2.7 mm |
撮影 | 電子線照射量: 60 e/Å2 / フィルム・検出器のモデル: GATAN K3 (6k x 4k) |
-解析
EMソフトウェア | 名称: cryoSPARC / カテゴリ: 3次元再構成 |
---|---|
CTF補正 | タイプ: NONE |
3次元再構成 | 解像度: 4.23 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 264487 / 対称性のタイプ: POINT |