+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 7tes | |||||||||
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タイトル | Cryo-EM structure of GluN1b-2B NMDAR in complex with Fab5 in Non-active1 conformation | |||||||||
要素 |
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キーワード | SIGNALING PROTEIN/IMMUNE SYSTEM / channel / antibody / 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 / regulation of postsynaptic cytosolic calcium ion concentration / sensory organ development / sensitization / pons maturation / regulation of cell communication / positive regulation of Schwann cell migration ...neurotransmitter receptor activity involved in regulation of postsynaptic membrane potential / cellular response to curcumin / cellular response to corticosterone stimulus / cellular response to magnesium starvation / regulation of postsynaptic cytosolic calcium ion concentration / sensory organ development / sensitization / 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 / response to hydrogen sulfide / Assembly and cell surface presentation of NMDA receptors / olfactory learning / regulation of protein kinase A signaling / conditioned taste aversion / apical dendrite / dendritic branch / regulation of respiratory gaseous exchange / positive regulation of inhibitory postsynaptic potential / response to other organism / protein localization to postsynaptic membrane / regulation of ARF protein signal transduction / response to methylmercury / fear response / propylene metabolic process / response to glycine / positive regulation of cysteine-type endopeptidase activity / cellular response to dsRNA / response to carbohydrate / negative regulation of dendritic spine maintenance / interleukin-1 receptor binding / voltage-gated monoatomic cation channel activity / cellular response to lipid / regulation of monoatomic cation transmembrane transport / positive regulation of glutamate secretion / response to morphine / response to growth hormone / NMDA glutamate receptor activity / Synaptic adhesion-like molecules / RAF/MAP kinase cascade / parallel fiber to Purkinje cell synapse / NMDA selective glutamate receptor complex / response to manganese ion / NMDA selective glutamate receptor signaling pathway / calcium ion transmembrane import into cytosol / neuromuscular process / glutamate binding / protein heterotetramerization / positive regulation of reactive oxygen species biosynthetic process / regulation of synapse assembly / regulation of axonogenesis / regulation of dendrite morphogenesis / positive regulation of calcium ion transport into cytosol / male mating behavior / glycine binding / heterocyclic compound binding / receptor clustering / suckling behavior / behavioral response to pain / startle response / response to amine / small molecule binding / action potential / : / monoatomic cation transmembrane transport / regulation of neuronal synaptic plasticity / monoatomic cation transport / associative learning / regulation of MAPK cascade / positive regulation of excitatory postsynaptic potential / social behavior / response to magnesium ion / cellular response to organic cyclic compound / ligand-gated monoatomic ion channel activity / extracellularly glutamate-gated ion channel activity / cellular response to glycine / excitatory synapse / positive regulation of dendritic spine maintenance / regulation of postsynaptic membrane potential / Unblocking of NMDA receptors, glutamate binding and activation / phosphatase binding / behavioral fear response / neuron development / postsynaptic density, intracellular component / cellular response to manganese ion / glutamate receptor binding / multicellular organismal response to stress / long-term memory / detection of mechanical stimulus involved in sensory perception of pain / prepulse inhibition / D2 dopamine receptor binding / monoatomic cation channel activity / calcium ion homeostasis / regulation of neuron apoptotic process / response to electrical stimulus / synaptic cleft / response to mechanical stimulus / glutamate-gated receptor activity 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: 4.7 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 | 7tes.cif.gz | 689.2 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb7tes.ent.gz | 575.7 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 7tes.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 | 7tes_validation.pdf.gz | 1 MB | 表示 | wwPDB検証レポート |
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文書・詳細版 | 7tes_full_validation.pdf.gz | 1.1 MB | 表示 | |
XML形式データ | 7tes_validation.xml.gz | 109.9 KB | 表示 | |
CIF形式データ | 7tes_validation.cif.gz | 165.6 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/te/7tes ftp://data.pdbj.org/pub/pdb/validation_reports/te/7tes | HTTPS FTP |
-関連構造データ
関連構造データ | 25851MC 7te4C 7te6C 7te9C 7tebC 7teeC 7teqC 7terC 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 |
-リンク
-集合体
登録構造単位 |
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1 |
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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: 抗体 | 分子量: 23844.684 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: 23855.256 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 complexed to Fab5 / タイプ: COMPLEX / Entity ID: all / 由来: MULTIPLE SOURCES |
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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): 3000 nm / 最小 デフォーカス(公称値): 1500 nm |
撮影 | 電子線照射量: 60 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: 4.7 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 53467 / 対称性のタイプ: POINT |