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データを開く
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基本情報
登録情報 | データベース: PDB / ID: 6xey | |||||||||
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タイトル | Cryo-EM structure of the SARS-CoV-2 spike glycoprotein bound to Fab 2-4 | |||||||||
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![]() | VIRAL PROTEIN/Immune System / spike / glycoprotein / antibody / VIRAL PROTEIN / VIRAL PROTEIN-Immune System complex | |||||||||
機能・相同性 | ![]() Maturation of spike protein / viral translation / Translation of Structural Proteins / Virion Assembly and Release / host cell surface / host extracellular space / suppression by virus of host tetherin activity / Induction of Cell-Cell Fusion / structural constituent of virion / entry receptor-mediated virion attachment to host cell ...Maturation of spike protein / viral translation / Translation of Structural Proteins / Virion Assembly and Release / host cell surface / host extracellular space / suppression by virus of host tetherin activity / Induction of Cell-Cell Fusion / structural constituent of virion / entry receptor-mediated virion attachment to host cell / host cell endoplasmic reticulum-Golgi intermediate compartment membrane / receptor-mediated endocytosis of virus by host cell / membrane fusion / Attachment and Entry / positive regulation of viral entry into host cell / receptor-mediated virion attachment to host cell / receptor ligand activity / host cell surface receptor binding / fusion of virus membrane with host plasma membrane / fusion of virus membrane with host endosome membrane / viral envelope / virion attachment to host cell / SARS-CoV-2 activates/modulates innate and adaptive immune responses / host cell plasma membrane / virion membrane / identical protein binding / membrane / plasma membrane 類似検索 - 分子機能 | |||||||||
生物種 | ![]() ![]() ![]() | |||||||||
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: 3.25 Å | |||||||||
![]() | Rapp, M. / Shapiro, L. / Ho, D.D. | |||||||||
資金援助 | ![]()
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![]() | ![]() タイトル: Potent neutralizing antibodies against multiple epitopes on SARS-CoV-2 spike. 著者: Lihong Liu / Pengfei Wang / Manoj S Nair / Jian Yu / Micah Rapp / Qian Wang / Yang Luo / Jasper F-W Chan / Vincent Sahi / Amir Figueroa / Xinzheng V Guo / Gabriele Cerutti / Jude Bimela / ...著者: Lihong Liu / Pengfei Wang / Manoj S Nair / Jian Yu / Micah Rapp / Qian Wang / Yang Luo / Jasper F-W Chan / Vincent Sahi / Amir Figueroa / Xinzheng V Guo / Gabriele Cerutti / Jude Bimela / Jason Gorman / Tongqing Zhou / Zhiwei Chen / Kwok-Yung Yuen / Peter D Kwong / Joseph G Sodroski / Michael T Yin / Zizhang Sheng / Yaoxing Huang / Lawrence Shapiro / David D Ho / ![]() ![]() 要旨: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic continues, with devasting consequences for human lives and the global economy. The discovery and development of virus- ...The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic continues, with devasting consequences for human lives and the global economy. The discovery and development of virus-neutralizing monoclonal antibodies could be one approach to treat or prevent infection by this coronavirus. Here we report the isolation of sixty-one SARS-CoV-2-neutralizing monoclonal antibodies from five patients infected with SARS-CoV-2 and admitted to hospital with severe coronavirus disease 2019 (COVID-19). Among these are nineteen antibodies that potently neutralized authentic SARS-CoV-2 in vitro, nine of which exhibited very high potency, with 50% virus-inhibitory concentrations of 0.7 to 9 ng ml. Epitope mapping showed that this collection of nineteen antibodies was about equally divided between those directed against the receptor-binding domain (RBD) and those directed against the N-terminal domain (NTD), indicating that both of these regions at the top of the viral spike are immunogenic. In addition, two other powerful neutralizing antibodies recognized quaternary epitopes that overlap with the domains at the top of the spike. Cryo-electron microscopy reconstructions of one antibody that targets the RBD, a second that targets the NTD, and a third that bridges two separate RBDs showed that the antibodies recognize the closed, 'all RBD-down' conformation of the spike. Several of these monoclonal antibodies are promising candidates for clinical development as potential therapeutic and/or prophylactic agents against SARS-CoV-2. #1: ![]() タイトル: Potent Neutralizing Antibodies Directed to Multiple Epitopes on SARS-CoV-2 Spike. 要旨: The SARS-CoV-2 pandemic rages on with devasting consequences on human lives and the global economy . The discovery and development of virus-neutralizing monoclonal antibodies could be one approach ...The SARS-CoV-2 pandemic rages on with devasting consequences on human lives and the global economy . The discovery and development of virus-neutralizing monoclonal antibodies could be one approach to treat or prevent infection by this novel coronavirus. Here we report the isolation of 61 SARS-CoV-2-neutralizing monoclonal antibodies from 5 infected patients hospitalized with severe disease. Among these are 19 antibodies that potently neutralized the authentic SARS-CoV-2 , 9 of which exhibited exquisite potency, with 50% virus-inhibitory concentrations of 0.7 to 9 ng/mL. Epitope mapping showed this collection of 19 antibodies to be about equally divided between those directed to the receptor-binding domain (RBD) and those to the N-terminal domain (NTD), indicating that both of these regions at the top of the viral spike are immunogenic. In addition, two other powerful neutralizing antibodies recognized quaternary epitopes that are overlapping with the domains at the top of the spike. Cryo-electron microscopy reconstructions of one antibody targeting RBD, a second targeting NTD, and a third bridging two separate RBDs revealed recognition of the closed, "all RBD-down" conformation of the spike. Several of these monoclonal antibodies are promising candidates for clinical development as potential therapeutic and/or prophylactic agents against SARS-CoV-2. | |||||||||
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構造の表示
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構造ビューア | 分子: ![]() ![]() |
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ダウンロードとリンク
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ダウンロード
PDBx/mmCIF形式 | ![]() | 649.5 KB | 表示 | ![]() |
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PDB形式 | ![]() | 536.7 KB | 表示 | ![]() |
PDBx/mmJSON形式 | ![]() | ツリー表示 | ![]() | |
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-検証レポート
文書・要旨 | ![]() | 1.9 MB | 表示 | ![]() |
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文書・詳細版 | ![]() | 1.9 MB | 表示 | |
XML形式データ | ![]() | 109.1 KB | 表示 | |
CIF形式データ | ![]() | 167.6 KB | 表示 | |
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-関連構造データ
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リンク
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集合体
登録構造単位 | ![]()
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要素
-タンパク質 , 1種, 3分子 ABC
#1: タンパク質 | 分子量: 142399.375 Da / 分子数: 3 / 由来タイプ: 組換発現 由来: (組換発現) ![]() ![]() 遺伝子: S, 2 / 発現宿主: ![]() |
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-抗体 , 2種, 6分子 FHJGKL
#2: 抗体 | 分子量: 13711.394 Da / 分子数: 3 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() #3: 抗体 | 分子量: 11400.429 Da / 分子数: 3 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() |
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-糖 , 4種, 48分子 ![](data/chem/img/NAG.gif)
#4: 多糖 | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose #5: 多糖 | #6: 多糖 | #7: 糖 | ChemComp-NAG / |
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-詳細
研究の焦点であるリガンドがあるか | N |
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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 |
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試料調製
構成要素 | 名称: SARS-CoV-2 spike glycoprotein bound to Fab 2-4 / タイプ: COMPLEX / Entity ID: #1-#3 / 由来: MULTIPLE SOURCES | ||||||||||||
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分子量 | 値: 515.96 kDa/nm / 実験値: NO | ||||||||||||
由来(天然) |
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緩衝液 | pH: 5.5 | ||||||||||||
試料 | 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES | ||||||||||||
急速凍結 | 装置: LEICA EM GP / 凍結剤: ETHANE / 湿度: 95 % / 凍結前の試料温度: 266 K |
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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: ![]() |
電子レンズ | モード: BRIGHT FIELD / 倍率(公称値): 81000 X / Cs: 2.7 mm |
撮影 | 電子線照射量: 51.3 e/Å2 フィルム・検出器のモデル: GATAN K3 BIOQUANTUM (6k x 4k) 撮影したグリッド数: 1 / 実像数: 3576 |
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解析
ソフトウェア | 名称: UCSF ChimeraX / バージョン: 0.93/v8 / 分類: モデル構築 / URL: https://www.rbvi.ucsf.edu/chimerax/ / Os: Windows / タイプ: package |
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CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION |
3次元再構成 | 解像度: 3.25 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 83927 / 対称性のタイプ: POINT |