+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 8vuh | ||||||||||||
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タイトル | Human GluN1-2A IgG 003-102 splayed conformation | ||||||||||||
要素 |
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キーワード | MEMBRANE/IMMUNE SYSTEM / Receptor / antibody / ion channel / MEMBRANE-IMMUNE SYSTEM complex | ||||||||||||
機能・相同性 | 機能・相同性情報 excitatory chemical synaptic transmission / directional locomotion / Synaptic adhesion-like molecules / serotonin metabolic process / protein localization to postsynaptic membrane / propylene metabolic process / response to glycine / sleep / activation of cysteine-type endopeptidase activity / Assembly and cell surface presentation of NMDA receptors ...excitatory chemical synaptic transmission / directional locomotion / Synaptic adhesion-like molecules / serotonin metabolic process / protein localization to postsynaptic membrane / propylene metabolic process / response to glycine / sleep / activation of cysteine-type endopeptidase activity / Assembly and cell surface presentation of NMDA receptors / regulation of monoatomic cation transmembrane transport / glutamate receptor signaling pathway / NMDA glutamate receptor activity / Neurexins and neuroligins / NMDA selective glutamate receptor complex / calcium ion transmembrane import into cytosol / glutamate binding / protein heterotetramerization / positive regulation of reactive oxygen species biosynthetic process / positive regulation of calcium ion transport into cytosol / glycine binding / dopamine metabolic process / Negative regulation of NMDA receptor-mediated neuronal transmission / Unblocking of NMDA receptors, glutamate binding and activation / startle response / monoatomic cation transmembrane transport / regulation of neuronal synaptic plasticity / monoatomic cation transport / Long-term potentiation / positive regulation of excitatory postsynaptic potential / ligand-gated monoatomic ion channel activity / excitatory synapse / calcium ion homeostasis / MECP2 regulates neuronal receptors and channels / synaptic cleft / glutamate-gated calcium ion channel activity / sensory perception of pain / EPHB-mediated forward signaling / Ras activation upon Ca2+ influx through NMDA receptor / response to amphetamine / ionotropic glutamate receptor signaling pathway / neurogenesis / positive regulation of synaptic transmission, glutamatergic / regulation of membrane potential / excitatory postsynaptic potential / transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential / synaptic membrane / synaptic transmission, glutamatergic / long-term synaptic potentiation / postsynaptic density membrane / negative regulation of protein catabolic process / visual learning / cytoplasmic vesicle membrane / protein catabolic process / brain development / regulation of synaptic plasticity / terminal bouton / memory / response to wounding / synaptic vesicle / signaling receptor activity / presynaptic membrane / amyloid-beta binding / RAF/MAP kinase cascade / chemical synaptic transmission / postsynaptic membrane / response to ethanol / dendritic spine / postsynaptic density / learning or memory / calmodulin binding / neuron projection / response to xenobiotic stimulus / positive regulation of apoptotic process / glutamatergic synapse / calcium ion binding / dendrite / synapse / endoplasmic reticulum membrane / protein-containing complex binding / cell surface / positive regulation of transcription by RNA polymerase II / zinc ion binding / plasma membrane / cytoplasm 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: 4.42 Å | ||||||||||||
データ登録者 | Michalski, K. / Furukawa, H. | ||||||||||||
資金援助 | 米国, 3件
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引用 | ジャーナル: Nat Struct Mol Biol / 年: 2024 タイトル: Structural and functional mechanisms of anti-NMDAR autoimmune encephalitis. 著者: Kevin Michalski / Taha Abdulla / Sam Kleeman / Lars Schmidl / Ricardo Gómez / Noriko Simorowski / Francesca Vallese / Harald Prüss / Manfred Heckmann / Christian Geis / Hiro Furukawa / 要旨: Autoantibodies against neuronal membrane proteins can manifest in autoimmune encephalitis, inducing seizures, cognitive dysfunction and psychosis. Anti-N-methyl-D-aspartate receptor (NMDAR) ...Autoantibodies against neuronal membrane proteins can manifest in autoimmune encephalitis, inducing seizures, cognitive dysfunction and psychosis. Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is the most dominant autoimmune encephalitis; however, insights into how autoantibodies recognize and alter receptor functions remain limited. Here we determined structures of human and rat NMDARs bound to three distinct patient-derived antibodies using single-particle electron cryo-microscopy. These antibodies bind different regions within the amino-terminal domain of the GluN1 subunit. Through electrophysiology, we show that all three autoantibodies acutely and directly reduced NMDAR channel functions in primary neurons. Antibodies show different stoichiometry of binding and antibody-receptor complex formation, which in one antibody, 003-102, also results in reduced synaptic localization of NMDARs. These studies demonstrate mechanisms of diverse epitope recognition and direct channel regulation of anti-NMDAR autoantibodies underlying autoimmune encephalitis. | ||||||||||||
履歴 |
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-構造の表示
構造ビューア | 分子: MolmilJmol/JSmol |
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-ダウンロードとリンク
-ダウンロード
PDBx/mmCIF形式 | 8vuh.cif.gz | 598.1 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb8vuh.ent.gz | 468.9 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 8vuh.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 | 8vuh_validation.pdf.gz | 1.4 MB | 表示 | wwPDB検証レポート |
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文書・詳細版 | 8vuh_full_validation.pdf.gz | 1.4 MB | 表示 | |
XML形式データ | 8vuh_validation.xml.gz | 104.7 KB | 表示 | |
CIF形式データ | 8vuh_validation.cif.gz | 158.8 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/vu/8vuh ftp://data.pdbj.org/pub/pdb/validation_reports/vu/8vuh | HTTPS FTP |
-関連構造データ
関連構造データ | 43530MC 8vujC 8vulC 8vunC 8vuqC 8vurC 8vusC 8vutC 8vuuC 8vuvC 8vuyC 8vvhC 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 | 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 |
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1 |
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-要素
#1: タンパク質 | 分子量: 91680.750 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: GRIN1, NMDAR1 発現宿主: Spodoptera frugiperda (ツマジロクサヨトウ) 参照: UniProt: Q05586 | ||||||
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#2: タンパク質 | 分子量: 90684.805 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: GRIN2A, NMDAR2A 発現宿主: Spodoptera frugiperda (ツマジロクサヨトウ) 参照: UniProt: Q12879 #3: タンパク質 | | 分子量: 91837.000 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: GRIN1, NMDAR1 発現宿主: Spodoptera frugiperda (ツマジロクサヨトウ) 参照: UniProt: Q05586 #4: 抗体 | 分子量: 12678.098 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 発現宿主: Homo sapiens (ヒト) #5: 抗体 | 分子量: 11681.605 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 発現宿主: Homo sapiens (ヒト) |
-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: Human GluN1-2A IgG 003-102 splayed conformation / タイプ: COMPLEX / Entity ID: all / 由来: RECOMBINANT |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
由来(組換発現) | 生物種: Homo sapiens (ヒト) |
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
顕微鏡 | モデル: FEI TITAN |
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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 |
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
CTF補正 | タイプ: NONE |
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3次元再構成 | 解像度: 4.42 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 101287 / 対称性のタイプ: POINT |