+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 7tee | |||||||||
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タイトル | Cryo-EM structure of GluN1b-2B NMDAR complexed to Fab2 Non-active2-like | |||||||||
要素 |
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キーワード | SIGNALING PROTEIN/IMMUNE SYSTEM / Channel / antibody (抗体) / SIGNALING PROTEIN-IMMUNE SYSTEM complex | |||||||||
機能・相同性 | 機能・相同性情報 neurotransmitter receptor activity involved in regulation of postsynaptic membrane potential / cellular response to curcumin / cellular response to corticosterone stimulus / cellular response to magnesium starvation / NMDA selective glutamate receptor signaling pathway / regulation of postsynaptic cytosolic calcium ion concentration / sensory organ development / 感作 / pons maturation / regulation of cell communication ...neurotransmitter receptor activity involved in regulation of postsynaptic membrane potential / cellular response to curcumin / cellular response to corticosterone stimulus / cellular response to magnesium starvation / NMDA selective glutamate receptor signaling pathway / regulation of postsynaptic cytosolic calcium ion concentration / sensory organ development / 感作 / pons maturation / regulation of cell communication / positive regulation of Schwann cell migration / EPHB-mediated forward signaling / neurotransmitter receptor activity involved in regulation of postsynaptic cytosolic calcium ion concentration / Assembly and cell surface presentation of NMDA receptors / olfactory learning / regulation of protein kinase A signaling / conditioned taste aversion / protein localization to postsynaptic membrane / 樹状突起 / regulation of respiratory gaseous exchange / propylene metabolic process / response to glycine / apical dendrite / response to other organism / fear response / response to methylmercury / voltage-gated monoatomic cation channel activity / positive regulation of cysteine-type endopeptidase activity / response to morphine / glutamate-gated calcium ion channel activity / cellular response to dsRNA / regulation of monoatomic cation transmembrane transport / response to carbohydrate / negative regulation of dendritic spine maintenance / interleukin-1 receptor binding / cellular response to lipid / positive regulation of glutamate secretion / NMDA glutamate receptor activity / response to growth hormone / NMDA selective glutamate receptor complex / RAF/MAP kinase cascade / Synaptic adhesion-like molecules / parallel fiber to Purkinje cell synapse / calcium ion transmembrane import into cytosol / response to manganese ion / protein heterotetramerization / glutamate binding / positive regulation of reactive oxygen species biosynthetic process / neuromuscular process / regulation of synapse assembly / 活動電位 / glycine binding / positive regulation of calcium ion transport into cytosol / male mating behavior / regulation of dendrite morphogenesis / regulation of axonogenesis / heterocyclic compound binding / suckling behavior / receptor clustering / startle response / behavioral response to pain / regulation of neuronal synaptic plasticity / response to amine / monoatomic cation transmembrane transport / regulation of MAPK cascade / social behavior / small molecule binding / 学習 / positive regulation of excitatory postsynaptic potential / response to magnesium ion / monoatomic cation transport / ligand-gated monoatomic ion channel activity / excitatory synapse / extracellularly glutamate-gated ion channel activity / cellular response to organic cyclic compound / Unblocking of NMDA receptors, glutamate binding and activation / positive regulation of dendritic spine maintenance / neuron development / glutamate receptor binding / regulation of postsynaptic membrane potential / multicellular organismal response to stress / phosphatase binding / behavioral fear response / calcium ion homeostasis / cellular response to manganese ion / D2 dopamine receptor binding / prepulse inhibition / long-term memory / detection of mechanical stimulus involved in sensory perception of pain / positive regulation of synaptic transmission / response to mechanical stimulus / regulation of neuron apoptotic process / response to electrical stimulus / synaptic cleft / presynaptic active zone membrane / glutamate-gated receptor activity / response to fungicide / cellular response to forskolin / monoatomic cation channel activity / sensory perception of pain 類似検索 - 分子機能 | |||||||||
生物種 | Rattus norvegicus (ドブネズミ) Mus musculus (ハツカネズミ) | |||||||||
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: 6.59 Å | |||||||||
データ登録者 | Tajima, N. / Furukawa, H. | |||||||||
資金援助 | 米国, 2件
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引用 | ジャーナル: Nat Commun / 年: 2022 タイトル: Development and characterization of functional antibodies targeting NMDA receptors. 著者: Nami Tajima / Noriko Simorowski / Remy A Yovanno / Michael C Regan / Kevin Michalski / Ricardo Gómez / Albert Y Lau / Hiro Furukawa / 要旨: N-methyl-D-aspartate receptors (NMDARs) are critically involved in basic brain functions and neurodegeneration as well as tumor invasiveness. Targeting specific subtypes of NMDARs with distinct ...N-methyl-D-aspartate receptors (NMDARs) are critically involved in basic brain functions and neurodegeneration as well as tumor invasiveness. Targeting specific subtypes of NMDARs with distinct activities has been considered an effective therapeutic strategy for neurological disorders and diseases. However, complete elimination of off-target effects of small chemical compounds has been challenging and thus, there is a need to explore alternative strategies for targeting NMDAR subtypes. Here we report identification of a functional antibody that specifically targets the GluN1-GluN2B NMDAR subtype and allosterically down-regulates ion channel activity as assessed by electrophysiology. Through biochemical analysis, x-ray crystallography, single-particle electron cryomicroscopy, and molecular dynamics simulations, we show that this inhibitory antibody recognizes the amino terminal domain of the GluN2B subunit and increases the population of the non-active conformational state. The current study demonstrates that antibodies may serve as specific reagents to regulate NMDAR functions for basic research and therapeutic objectives. | |||||||||
履歴 |
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-構造の表示
ムービー |
ムービービューア |
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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 | 7tee.cif.gz | 629.5 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb7tee.ent.gz | 519.5 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 7tee.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
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/te/7tee ftp://data.pdbj.org/pub/pdb/validation_reports/te/7tee | HTTPS FTP |
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-関連構造データ
関連構造データ | 25845MC 7te4C 7te6C 7te9C 7tebC 7teqC 7terC 7tesC 7tetC 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) |
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類似構造データ | |
その他のデータベース |
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-リンク
-集合体
登録構造単位 |
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-要素
#1: タンパク質 | 分子量: 96944.891 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) Rattus norvegicus (ドブネズミ) / 遺伝子: Grin1, Nmdar1 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: 98797.820 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) Rattus norvegicus (ドブネズミ) / 遺伝子: Grin2b 発現宿主: Spodoptera frugiperda (ツマジロクサヨトウ) 参照: UniProt: Q00960 #3: タンパク質 | 分子量: 23914.781 Da / 分子数: 2 / 由来タイプ: 天然 / 由来: (天然) Mus musculus (ハツカネズミ) #4: 抗体 | 分子量: 23572.031 Da / 分子数: 2 / 由来タイプ: 天然 / 由来: (天然) Mus musculus (ハツカネズミ) |
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-実験情報
-実験
実験 | 手法: 電子顕微鏡法 |
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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: GluN1b-2B NMDAR - Fab2 / タイプ: COMPLEX / Entity ID: all / 由来: MULTIPLE SOURCES |
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分子量 | 実験値: NO |
由来(天然) | 生物種: Rattus norvegicus (ドブネズミ) |
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 |
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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): 3500 nm / 最小 デフォーカス(公称値): 1000 nm |
撮影 | 電子線照射量: 65 e/Å2 フィルム・検出器のモデル: GATAN K3 BIOQUANTUM (6k x 4k) |
-解析
CTF補正 | タイプ: PHASE FLIPPING ONLY |
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3次元再構成 | 解像度: 6.59 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 18851 / 対称性のタイプ: POINT |