+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-21965 | |||||||||
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タイトル | Negative stain EM map of SARS CoV-2 spike protein (trimer) | |||||||||
マップデータ | SRAS Cov2 spike protein (trimer) | |||||||||
試料 |
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機能・相同性 | 機能・相同性情報 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 / host cell endoplasmic reticulum-Golgi intermediate compartment membrane ...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 / host cell endoplasmic reticulum-Golgi intermediate compartment membrane / entry receptor-mediated virion attachment to host cell / receptor-mediated endocytosis of virus by host cell / Attachment and Entry / membrane fusion / 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 / エンベロープ (ウイルス) / symbiont-mediated suppression of host type I interferon-mediated signaling pathway / virion attachment to host cell / SARS-CoV-2 activates/modulates innate and adaptive immune responses / host cell plasma membrane / virion membrane / 生体膜 / identical protein binding / 細胞膜 類似検索 - 分子機能 | |||||||||
生物種 | Severe acute respiratory syndrome coronavirus 2 (SARSコロナウイルス2) | |||||||||
手法 | 単粒子再構成法 / ネガティブ染色法 / 解像度: 20.0 Å | |||||||||
データ登録者 | Binshtein E | |||||||||
資金援助 | 米国, 2件
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引用 | ジャーナル: Nature / 年: 2020 タイトル: Potently neutralizing and protective human antibodies against SARS-CoV-2. 著者: Seth J Zost / Pavlo Gilchuk / James Brett Case / Elad Binshtein / Rita E Chen / Joseph P Nkolola / Alexandra Schäfer / Joseph X Reidy / Andrew Trivette / Rachel S Nargi / Rachel E Sutton / ...著者: Seth J Zost / Pavlo Gilchuk / James Brett Case / Elad Binshtein / Rita E Chen / Joseph P Nkolola / Alexandra Schäfer / Joseph X Reidy / Andrew Trivette / Rachel S Nargi / Rachel E Sutton / Naveenchandra Suryadevara / David R Martinez / Lauren E Williamson / Elaine C Chen / Taylor Jones / Samuel Day / Luke Myers / Ahmed O Hassan / Natasha M Kafai / Emma S Winkler / Julie M Fox / Swathi Shrihari / Benjamin K Mueller / Jens Meiler / Abishek Chandrashekar / Noe B Mercado / James J Steinhardt / Kuishu Ren / Yueh-Ming Loo / Nicole L Kallewaard / Broc T McCune / Shamus P Keeler / Michael J Holtzman / Dan H Barouch / Lisa E Gralinski / Ralph S Baric / Larissa B Thackray / Michael S Diamond / Robert H Carnahan / James E Crowe / 要旨: The ongoing pandemic of coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a major threat to global health and the medical ...The ongoing pandemic of coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a major threat to global health and the medical countermeasures available so far are limited. Moreover, we currently lack a thorough understanding of the mechanisms of humoral immunity to SARS-CoV-2. Here we analyse a large panel of human monoclonal antibodies that target the spike (S) glycoprotein, and identify several that exhibit potent neutralizing activity and fully block the receptor-binding domain of the S protein (S) from interacting with human angiotensin-converting enzyme 2 (ACE2). Using competition-binding, structural and functional studies, we show that the monoclonal antibodies can be clustered into classes that recognize distinct epitopes on the S, as well as distinct conformational states of the S trimer. Two potently neutralizing monoclonal antibodies, COV2-2196 and COV2-2130, which recognize non-overlapping sites, bound simultaneously to the S protein and neutralized wild-type SARS-CoV-2 virus in a synergistic manner. In two mouse models of SARS-CoV-2 infection, passive transfer of COV2-2196, COV2-2130 or a combination of both of these antibodies protected mice from weight loss and reduced the viral burden and levels of inflammation in the lungs. In addition, passive transfer of either of two of the most potent ACE2-blocking monoclonal antibodies (COV2-2196 or COV2-2381) as monotherapy protected rhesus macaques from SARS-CoV-2 infection. These results identify protective epitopes on the S and provide a structure-based framework for rational vaccine design and the selection of robust immunotherapeutic agents. | |||||||||
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 | EMマップ: SurfViewMolmilJmol/JSmol |
添付画像 |
-ダウンロードとリンク
-EMDBアーカイブ
マップデータ | emd_21965.map.gz | 4 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-21965-v30.xml emd-21965.xml | 12.9 KB 12.9 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_21965.png | 26.3 KB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-21965 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-21965 | HTTPS FTP |
-関連構造データ
関連構造データ | C: 同じ文献を引用 (文献) |
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類似構造データ |
-リンク
EMDBのページ | EMDB (EBI/PDBe) / EMDataResource |
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「今月の分子」の関連する項目 |
-マップ
ファイル | ダウンロード / ファイル: emd_21965.map.gz / 形式: CCP4 / 大きさ: 8 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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注釈 | SRAS Cov2 spike protein (trimer) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 4.36 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
密度 |
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対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
詳細 | EMDB XML:
CCP4マップ ヘッダ情報:
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-添付データ
-試料の構成要素
-全体 : SARS CoV-2 spike protein (trimer)
全体 | 名称: SARS CoV-2 spike protein (trimer) |
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要素 |
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-超分子 #1: SARS CoV-2 spike protein (trimer)
超分子 | 名称: SARS CoV-2 spike protein (trimer) / タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1 |
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由来(天然) | 生物種: Severe acute respiratory syndrome coronavirus 2 (SARSコロナウイルス2) |
組換発現 | 生物種: Homo sapiens (ヒト) |
-実験情報
-構造解析
手法 | ネガティブ染色法 |
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解析 | 単粒子再構成法 |
試料の集合状態 | particle |
-試料調製
濃度 | 0.01 mg/mL | ||||||
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緩衝液 | pH: 8 構成要素:
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染色 | タイプ: NEGATIVE / 材質: UF | ||||||
グリッド | 材質: COPPER / メッシュ: 400 |
-電子顕微鏡法
顕微鏡 | FEI TECNAI F20 |
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電子線 | 加速電圧: 200 kV / 電子線源: FIELD EMISSION GUN |
電子光学系 | C2レンズ絞り径: 100.0 µm / 照射モード: OTHER / 撮影モード: BRIGHT FIELDBright-field microscopy / Cs: 2.2 mm / 最大 デフォーカス(公称値): 1.9 µm / 最小 デフォーカス(公称値): 1.5 µm / 倍率(公称値): 50000 |
試料ステージ | 試料ホルダーモデル: SIDE ENTRY, EUCENTRIC |
撮影 | フィルム・検出器のモデル: GATAN ULTRASCAN 4000 (4k x 4k) 撮影したグリッド数: 1 / 実像数: 122 / 平均電子線量: 25.0 e/Å2 |
実験機器 | モデル: Tecnai F20 / 画像提供: FEI Company |
-画像解析
粒子像選択 | 選択した数: 3585 |
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CTF補正 | ソフトウェア - 名称: cryoSPARC (ver. 2.14.2) |
初期 角度割当 | タイプ: NOT APPLICABLE |
最終 角度割当 | タイプ: NOT APPLICABLE |
最終 再構成 | 解像度のタイプ: BY AUTHOR / 解像度: 20.0 Å / 解像度の算出法: FSC 0.143 CUT-OFF / ソフトウェア - 名称: cryoSPARC (ver. 2.14.2) / 使用した粒子像数: 2188 |