+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 7teq | |||||||||
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タイトル | Cryo-EM structure of GluN1b-2B NMDAR in complex with Fab5 active 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 / Assembly and cell surface presentation of NMDA receptors / response to hydrogen sulfide / olfactory learning / regulation of protein kinase A signaling / conditioned taste aversion / dendritic branch / regulation of respiratory gaseous exchange / protein localization to postsynaptic membrane / response to other organism / positive regulation of inhibitory postsynaptic potential / apical dendrite / propylene metabolic process / response to glycine / regulation of ARF protein signal transduction / fear response / response to methylmercury / voltage-gated monoatomic cation channel activity / positive regulation of cysteine-type endopeptidase activity / cellular response to dsRNA / response to carbohydrate / negative regulation of dendritic spine maintenance / regulation of monoatomic cation transmembrane transport / interleukin-1 receptor binding / cellular response to lipid / response to morphine / NMDA glutamate receptor activity / positive regulation of glutamate secretion / response to growth hormone / Synaptic adhesion-like molecules / NMDA selective glutamate receptor complex / RAF/MAP kinase cascade / parallel fiber to Purkinje cell synapse / response to manganese ion / NMDA selective glutamate receptor signaling pathway / calcium ion transmembrane import into cytosol / glutamate-gated calcium ion channel activity / glutamate binding / neuromuscular process / positive regulation of reactive oxygen species biosynthetic process / protein heterotetramerization / regulation of synapse assembly / action potential / glycine binding / positive regulation of calcium ion transport into cytosol / regulation of dendrite morphogenesis / regulation of axonogenesis / male mating behavior / heterocyclic compound binding / suckling behavior / startle response / behavioral response to pain / response to amine / monoatomic cation transmembrane transport / receptor clustering / monoatomic cation transport / regulation of neuronal synaptic plasticity / associative learning / positive regulation of excitatory postsynaptic potential / regulation of MAPK cascade / social behavior / response to magnesium ion / ligand-gated monoatomic ion channel activity / cellular response to organic cyclic compound / extracellularly glutamate-gated ion channel activity / cellular response to glycine / excitatory synapse / positive regulation of dendritic spine maintenance / small molecule binding / neuron development / Unblocking of NMDA receptors, glutamate binding and activation / behavioral fear response / regulation of postsynaptic membrane potential / postsynaptic density, intracellular component / phosphatase binding / cellular response to manganese ion / calcium ion homeostasis / glutamate receptor binding / D2 dopamine receptor binding / prepulse inhibition / multicellular organismal response to stress / monoatomic cation channel activity / long-term memory / detection of mechanical stimulus involved in sensory perception of pain / regulation of neuron apoptotic process / response to electrical stimulus / synaptic cleft / glutamate-gated receptor activity / presynaptic active zone membrane 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: 7.51 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 | 7teq.cif.gz | 610.1 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb7teq.ent.gz | 503.8 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 7teq.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 | 7teq_validation.pdf.gz | 1 MB | 表示 | wwPDB検証レポート |
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文書・詳細版 | 7teq_full_validation.pdf.gz | 1.1 MB | 表示 | |
XML形式データ | 7teq_validation.xml.gz | 99.5 KB | 表示 | |
CIF形式データ | 7teq_validation.cif.gz | 147.4 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/te/7teq ftp://data.pdbj.org/pub/pdb/validation_reports/te/7teq | HTTPS FTP |
-関連構造データ
関連構造データ | 25849MC 7te4C 7te6C 7te9C 7tebC 7teeC 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 |
-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: 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: 23121.395 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 |
試料支持 | グリッドのタイプ: C-flat-1.2/1.3 |
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: 7.51 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 13386 / 対称性のタイプ: POINT |