+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 7nrh | ||||||
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タイトル | Hantaan virus glycoprotein (Gn) in complex with Fab fragment HTN-Gn1. | ||||||
要素 |
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キーワード | VIRUS LIKE PARTICLE / VLP / virus-like particle / Hantaan / HTNV / HNTV / glycoprotein / spike / fab / HTN-Gn1 / antibody / epitope | ||||||
機能・相同性 | 機能・相同性情報 symbiont-mediated suppression of host TRAF-mediated signal transduction / host cell Golgi membrane / host cell mitochondrion / host cell surface / host cell endoplasmic reticulum membrane / symbiont-mediated suppression of host innate immune response / virus-mediated perturbation of host defense response / virion membrane / cell surface / signal transduction ...symbiont-mediated suppression of host TRAF-mediated signal transduction / host cell Golgi membrane / host cell mitochondrion / host cell surface / host cell endoplasmic reticulum membrane / symbiont-mediated suppression of host innate immune response / virus-mediated perturbation of host defense response / virion membrane / cell surface / signal transduction / membrane / metal ion binding 類似検索 - 分子機能 | ||||||
生物種 | Oryctolagus cuniculus (ウサギ) Hantaan orthohantavirus (ウイルス) | ||||||
手法 | 電子顕微鏡法 / サブトモグラム平均法 / クライオ電子顕微鏡法 / 解像度: 19 Å | ||||||
データ登録者 | Stass, R. / Rissanen, I. / Bowden, T.A. / Huiskonen, J.T. | ||||||
資金援助 | 英国, 1件
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引用 | ジャーナル: mBio / 年: 2021 タイトル: Structural Basis for a Neutralizing Antibody Response Elicited by a Recombinant Hantaan Virus Gn Immunogen. 著者: Ilona Rissanen / Stefanie A Krumm / Robert Stass / Annalis Whitaker / James E Voss / Emily A Bruce / Sylvia Rothenberger / Stefan Kunz / Dennis R Burton / Juha T Huiskonen / Jason W Botten / ...著者: Ilona Rissanen / Stefanie A Krumm / Robert Stass / Annalis Whitaker / James E Voss / Emily A Bruce / Sylvia Rothenberger / Stefan Kunz / Dennis R Burton / Juha T Huiskonen / Jason W Botten / Thomas A Bowden / Katie J Doores / 要旨: Hantaviruses are a group of emerging pathogens capable of causing severe disease upon zoonotic transmission to humans. The mature hantavirus surface presents higher-order tetrameric assemblies of two ...Hantaviruses are a group of emerging pathogens capable of causing severe disease upon zoonotic transmission to humans. The mature hantavirus surface presents higher-order tetrameric assemblies of two glycoproteins, Gn and Gc, which are responsible for negotiating host cell entry and constitute key therapeutic targets. Here, we demonstrate that recombinantly derived Gn from Hantaan virus (HTNV) elicits a neutralizing antibody response (serum dilution that inhibits 50% infection [ID], 1:200 to 1:850) in an animal model. Using antigen-specific B cell sorting, we isolated monoclonal antibodies (mAbs) exhibiting neutralizing and non-neutralizing activity, termed mAb HTN-Gn1 and mAb nnHTN-Gn2, respectively. Crystallographic analysis reveals that these mAbs target spatially distinct epitopes at disparate sites of the N-terminal region of the HTNV Gn ectodomain. Epitope mapping onto a model of the higher order (Gn-Gc) spike supports the immune accessibility of the mAb HTN-Gn1 epitope, a hypothesis confirmed by electron cryo-tomography of the antibody with virus-like particles. These data define natively exposed regions of the hantaviral Gn that can be targeted in immunogen design. The spillover of pathogenic hantaviruses from rodent reservoirs into the human population poses a continued threat to human health. Here, we show that a recombinant form of the Hantaan virus (HTNV) surface-displayed glycoprotein, Gn, elicits a neutralizing antibody response in rabbits. We isolated a neutralizing (HTN-Gn1) and a non-neutralizing (nnHTN-Gn2) monoclonal antibody and provide the first molecular-level insights into how the Gn glycoprotein may be targeted by the antibody-mediated immune response. These findings may guide rational vaccine design approaches focused on targeting the hantavirus glycoprotein envelope. | ||||||
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 | 7nrh.cif.gz | 312.5 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb7nrh.ent.gz | 264.3 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 7nrh.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/nr/7nrh ftp://data.pdbj.org/pub/pdb/validation_reports/nr/7nrh | HTTPS FTP |
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-関連構造データ
-リンク
-集合体
登録構造単位 |
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-要素
#1: 抗体 | 分子量: 24284.264 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Oryctolagus cuniculus (ウサギ) / 発現宿主: Homo sapiens (ヒト) |
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#2: 抗体 | 分子量: 22943.162 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Oryctolagus cuniculus (ウサギ) / 発現宿主: Homo sapiens (ヒト) |
#3: タンパク質 | 分子量: 40350.871 Da / 分子数: 1 / 由来タイプ: 組換発現 由来: (組換発現) Hantaan orthohantavirus (ウイルス) 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: A0A077D153 |
#4: 多糖 | alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-3)-alpha-D- ...alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-3)-alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose |
研究の焦点であるリガンドがあるか | N |
-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: サブトモグラム平均法 |
-試料調製
構成要素 | 名称: Hantaan orthohantavirus / タイプ: VIRUS / Entity ID: #1-#3 / 由来: RECOMBINANT |
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由来(天然) | 生物種: Hantaan orthohantavirus (ウイルス) |
由来(組換発現) | 生物種: Homo sapiens (ヒト) |
ウイルスについての詳細 | 中空か: YES / エンベロープを持つか: YES / 単離: SPECIES / タイプ: VIRUS-LIKE PARTICLE |
緩衝液 | pH: 7.5 / 詳細: PBS |
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-PROPANE |
-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 |
撮影 | 電子線照射量: 4.77 e/Å2 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 | 名称: Dynamo / カテゴリ: 3次元再構成 |
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CTF補正 | タイプ: PHASE FLIPPING ONLY |
対称性 | 点対称性: C1 (非対称) |
3次元再構成 | 解像度: 19 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 2380 / 対称性のタイプ: POINT |
EM volume selection | Num. of tomograms: 42 / Num. of volumes extracted: 34460 |