+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 8fe4 | |||||||||
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タイトル | Structure of dengue virus (DENV2) in complex with prM13, an anti-PrM monoclonal antibody | |||||||||
要素 |
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キーワード | VIRUS/IMMUNE SYSTEM / DENV / flavivirus / prM antibody / prM13 / VIRUS-IMMUNE SYSTEM complex | |||||||||
機能・相同性 | 機能・相同性情報 symbiont-mediated suppression of host JAK-STAT cascade via inhibition of host TYK2 activity / host cell mitochondrion / symbiont-mediated suppression of host JAK-STAT cascade via inhibition of STAT2 activity / symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of MAVS activity / ribonucleoside triphosphate phosphatase activity / viral capsid / double-stranded RNA binding / protein complex oligomerization / monoatomic ion channel activity / clathrin-dependent endocytosis of virus by host cell ...symbiont-mediated suppression of host JAK-STAT cascade via inhibition of host TYK2 activity / host cell mitochondrion / symbiont-mediated suppression of host JAK-STAT cascade via inhibition of STAT2 activity / symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of MAVS activity / ribonucleoside triphosphate phosphatase activity / viral capsid / double-stranded RNA binding / protein complex oligomerization / monoatomic ion channel activity / clathrin-dependent endocytosis of virus by host cell / mRNA (nucleoside-2'-O-)-methyltransferase activity / mRNA 5'-cap (guanine-N7-)-methyltransferase activity / RNA helicase activity / host cell endoplasmic reticulum membrane / protein dimerization activity / symbiont-mediated suppression of host type I interferon-mediated signaling pathway / induction by virus of host autophagy / serine-type endopeptidase activity / viral RNA genome replication / virus-mediated perturbation of host defense response / RNA-dependent RNA polymerase activity / fusion of virus membrane with host endosome membrane / viral envelope / virion attachment to host cell / structural molecule activity / virion membrane / proteolysis / extracellular region / ATP binding / membrane / metal ion binding 類似検索 - 分子機能 | |||||||||
生物種 | Dengue virus type 2 (デング熱ウイルス) 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: 9.8 Å | |||||||||
データ登録者 | Dowd, A.D. / Sirohi, D. / Speer, S. / Mukherjee, S. / Govero, J. / Aleshnick, M. / Larman, B. / Sukupolvi-Petty, S. / Sevvana, M. / Miller, A.S. ...Dowd, A.D. / Sirohi, D. / Speer, S. / Mukherjee, S. / Govero, J. / Aleshnick, M. / Larman, B. / Sukupolvi-Petty, S. / Sevvana, M. / Miller, A.S. / Klose, T. / Zheng, A. / Kielian, M. / Kuhn, R.J. / Diamond, M.S. / Pierson, T.C. | |||||||||
資金援助 | 米国, 2件
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引用 | ジャーナル: Proc Natl Acad Sci U S A / 年: 2023 タイトル: prM-reactive antibodies reveal a role for partially mature virions in dengue virus pathogenesis. 著者: Kimberly A Dowd / Devika Sirohi / Scott D Speer / Laura A VanBlargan / Rita E Chen / Swati Mukherjee / Bradley M Whitener / Jennifer Govero / Maya Aleshnick / Bridget Larman / Soila Sukupolvi- ...著者: Kimberly A Dowd / Devika Sirohi / Scott D Speer / Laura A VanBlargan / Rita E Chen / Swati Mukherjee / Bradley M Whitener / Jennifer Govero / Maya Aleshnick / Bridget Larman / Soila Sukupolvi-Petty / Madhumati Sevvana / Andrew S Miller / Thomas Klose / Aihua Zheng / Scott Koenig / Margaret Kielian / Richard J Kuhn / Michael S Diamond / Theodore C Pierson / 要旨: Cleavage of the flavivirus premembrane (prM) structural protein during maturation can be inefficient. The contribution of partially mature flavivirus virions that retain uncleaved prM to pathogenesis ...Cleavage of the flavivirus premembrane (prM) structural protein during maturation can be inefficient. The contribution of partially mature flavivirus virions that retain uncleaved prM to pathogenesis during primary infection is unknown. To investigate this question, we characterized the functional properties of newly-generated dengue virus (DENV) prM-reactive monoclonal antibodies (mAbs) in vitro and using a mouse model of DENV disease. Anti-prM mAbs neutralized DENV infection in a virion maturation state-dependent manner. Alanine scanning mutagenesis and cryoelectron microscopy of anti-prM mAbs in complex with immature DENV defined two modes of attachment to a single antigenic site. In vivo, passive transfer of intact anti-prM mAbs resulted in an antibody-dependent enhancement of disease. However, protection against DENV-induced lethality was observed when the transferred mAbs were genetically modified to inhibit their ability to interact with Fcγ receptors. These data establish that in addition to mature forms of the virus, partially mature infectious prM virions can also contribute to pathogenesis during primary DENV infections. | |||||||||
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 | 8fe4.cif.gz | 400.6 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb8fe4.ent.gz | 280.8 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 8fe4.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/fe/8fe4 ftp://data.pdbj.org/pub/pdb/validation_reports/fe/8fe4 | HTTPS FTP |
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-関連構造データ
関連構造データ | 29021MC 8fe3C 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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対称性 | 点対称性: (シェーンフリース記号: I (正20面体型対称)) |
-要素
#1: タンパク質 | 分子量: 43892.469 Da / 分子数: 3 / 由来タイプ: 組換発現 由来: (組換発現) Dengue virus type 2 (デング熱ウイルス) 細胞株 (発現宿主): C6/36 / 発現宿主: Aedes albopictus (ヒトスジシマカ) / 参照: UniProt: A0A481XTV0 #2: タンパク質 | 分子量: 9261.531 Da / 分子数: 3 / 由来タイプ: 組換発現 由来: (組換発現) Dengue virus type 2 (デング熱ウイルス) 細胞株 (発現宿主): C6/36 / 発現宿主: Aedes albopictus (ヒトスジシマカ) / 参照: UniProt: A0A481XTV0 #3: 抗体 | 分子量: 23777.656 Da / 分子数: 3 / Mutation: X1A,X2A / 由来タイプ: 組換発現 詳細: The homology model of the prM13 variable heavy chain domain (1-118) was pieced together with the crystal structure of the constant heavy chain domain, derived from ZV-67, which belongs to ...詳細: The homology model of the prM13 variable heavy chain domain (1-118) was pieced together with the crystal structure of the constant heavy chain domain, derived from ZV-67, which belongs to murine IgG2c isotype similar to prM13. 由来: (組換発現) Mus musculus (ハツカネズミ) / 細胞株 (発現宿主): HEK293T/17 / 発現宿主: Homo sapiens (ヒト) #4: 抗体 | 分子量: 23245.510 Da / 分子数: 3 / Mutation: X1A,X4A,X106A,X103A / 由来タイプ: 組換発現 詳細: The homology model of the prM13 variable light chain domain (1-106) was pieced together with the crystal structure of the constant light chain domain, derived from ZV-67, which belongs to ...詳細: The homology model of the prM13 variable light chain domain (1-106) was pieced together with the crystal structure of the constant light chain domain, derived from ZV-67, which belongs to murine IgG2c isotype similar to prM13. 由来: (組換発現) Mus musculus (ハツカネズミ) / 細胞株 (発現宿主): HEK293T/17 / 発現宿主: Homo sapiens (ヒト) |
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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: Mus musculus / タイプ: VIRUS / Entity ID: all / 由来: RECOMBINANT | ||||||||||||
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分子量 | 実験値: NO | ||||||||||||
由来(天然) |
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由来(組換発現) |
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ウイルスについての詳細 | 中空か: NO / エンベロープを持つか: YES / 単離: SEROTYPE / タイプ: VIRION | ||||||||||||
ウイルス殻 | 直径: 500 nm / 三角数 (T数): 3 | ||||||||||||
緩衝液 | pH: 8 | ||||||||||||
試料 | 濃度: 5 mg/ml / 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES | ||||||||||||
試料支持 | グリッドの材料: COPPER / グリッドのサイズ: 200 divisions/in. グリッドのタイプ: PELCO Ultrathin Carbon with Lacey Carbon | ||||||||||||
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: FLOOD BEAM |
電子レンズ | モード: BRIGHT FIELD / 倍率(公称値): 81000 X / 最大 デフォーカス(公称値): 2500 nm / 最小 デフォーカス(公称値): 1000 nm / Cs: 2.7 mm / C2レンズ絞り径: 100 µm / アライメント法: COMA FREE |
試料ホルダ | 凍結剤: NITROGEN 試料ホルダーモデル: FEI TITAN KRIOS AUTOGRID HOLDER |
撮影 | 電子線照射量: 30 e/Å2 / 検出モード: SUPER-RESOLUTION フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) |
-解析
EMソフトウェア |
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CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | |||||||||||||||||||||
対称性 | 点対称性: I (正20面体型対称) | |||||||||||||||||||||
3次元再構成 | 解像度: 9.8 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 5458 / 対称性のタイプ: POINT | |||||||||||||||||||||
原子モデル構築 | プロトコル: RIGID BODY FIT / 空間: REAL | |||||||||||||||||||||
原子モデル構築 |
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精密化 | 最高解像度: 9.8 Å |