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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: 7dcc | ||||||
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タイトル | S-3C1-F3b structure, all the three RBDs are in the up conformation and each of them associates with a 3C1 Fab | ||||||
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![]() | VIRAL PROTEIN | ||||||
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 / symbiont-mediated suppression of host innate immune response / 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: 4.3 Å | ||||||
![]() | Cong, Y. / Liu, C.X. | ||||||
資金援助 | ![]()
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![]() | ![]() タイトル: Development and structural basis of a two-MAb cocktail for treating SARS-CoV-2 infections. 著者: Chao Zhang / Yifan Wang / Yuanfei Zhu / Caixuan Liu / Chenjian Gu / Shiqi Xu / Yalei Wang / Yu Zhou / Yanxing Wang / Wenyu Han / Xiaoyu Hong / Yong Yang / Xueyang Zhang / Tingfeng Wang / Cong ...著者: Chao Zhang / Yifan Wang / Yuanfei Zhu / Caixuan Liu / Chenjian Gu / Shiqi Xu / Yalei Wang / Yu Zhou / Yanxing Wang / Wenyu Han / Xiaoyu Hong / Yong Yang / Xueyang Zhang / Tingfeng Wang / Cong Xu / Qin Hong / Shutian Wang / Qiaoyu Zhao / Weihua Qiao / Jinkai Zang / Liangliang Kong / Fangfang Wang / Haikun Wang / Di Qu / Dimitri Lavillette / Hong Tang / Qiang Deng / Youhua Xie / Yao Cong / Zhong Huang / ![]() 要旨: The ongoing pandemic of coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Neutralizing antibodies against SARS-CoV-2 are an option for ...The ongoing pandemic of coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Neutralizing antibodies against SARS-CoV-2 are an option for drug development for treating COVID-19. Here, we report the identification and characterization of two groups of mouse neutralizing monoclonal antibodies (MAbs) targeting the receptor-binding domain (RBD) on the SARS-CoV-2 spike (S) protein. MAbs 2H2 and 3C1, representing the two antibody groups, respectively, bind distinct epitopes and are compatible in formulating a noncompeting antibody cocktail. A humanized version of the 2H2/3C1 cocktail is found to potently neutralize authentic SARS-CoV-2 infection in vitro with half inhibitory concentration (IC50) of 12 ng/mL and effectively treat SARS-CoV-2-infected mice even when administered at as late as 24 h post-infection. We determine an ensemble of cryo-EM structures of 2H2 or 3C1 Fab in complex with the S trimer up to 3.8 Å resolution, revealing the conformational space of the antigen-antibody complexes and MAb-triggered stepwise allosteric rearrangements of the S trimer, delineating a previously uncharacterized dynamic process of coordinated binding of neutralizing antibodies to the trimeric S protein. Our findings provide important information for the development of MAb-based drugs for preventing and treating SARS-CoV-2 infections. | ||||||
履歴 |
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構造の表示
ムービー |
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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 | ![]() | 772.3 KB | 表示 | ![]() |
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PDB形式 | ![]() | 645.9 KB | 表示 | ![]() |
PDBx/mmJSON形式 | ![]() | ツリー表示 | ![]() | |
その他 | ![]() |
-検証レポート
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
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-関連構造データ
関連構造データ | ![]() 30635MC ![]() 7dcxC ![]() 7dd2C ![]() 7dd8C ![]() 7dddC ![]() 7ddnC ![]() 7dk4C ![]() 7dk5C ![]() 7dk6C ![]() 7dk7C 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 ( |
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類似構造データ |
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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
#1: 抗体 | 分子量: 24151.785 Da / 分子数: 3 / 由来タイプ: 天然 / 由来: (天然) ![]() ![]() #2: タンパク質 | 分子量: 140055.906 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 / 細胞株 (発現宿主): HEK293F / 発現宿主: ![]() #3: 抗体 | 分子量: 23891.330 Da / 分子数: 3 / 由来タイプ: 天然 / 由来: (天然) ![]() ![]() 配列の詳細 | In order to express SARS-CoV-2 S glycoprotein ectodomain, the mammalian codon-optimized gene coding ...In order to express SARS-CoV-2 S glycoprotein ectodomain, the mammalian codon-optimized gene coding SARS-CoV-2 S glycoprotein ectodomain (residues M1-Q1208) with proline substitutions at K986 and V987 which could make S protein more stable, a 'GSAS- substitution at the furin cleavage site (R682-R685) to avoid the furin cleavage. A C-terminal T4 fibritin trimerization motif, a TEV protease cleavage site, a FLAG tag and a His tag were cloned downstream of the SARS-CoV-2 S glycoprotein ectodomain (1209-1261). | |
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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 |
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由来(組換発現) | 生物種: ![]() | ||||||||||||||||||||||||
緩衝液 | pH: 7.5 | ||||||||||||||||||||||||
緩衝液成分 |
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試料 | 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES | ||||||||||||||||||||||||
試料支持 | 詳細: To handle the potential preferred orientation problem, for sample frozen using holey carbon grid, 0.05% Octyl beta-D-glucopyranoside (Sigma) or 0.1% polylysine (Polysciences) was added into ...詳細: To handle the potential preferred orientation problem, for sample frozen using holey carbon grid, 0.05% Octyl beta-D-glucopyranoside (Sigma) or 0.1% polylysine (Polysciences) was added into the sample or applied on grid before freezing, respectively. グリッドの材料: COPPER / グリッドのタイプ: Quantifoil | ||||||||||||||||||||||||
急速凍結 | 凍結剤: ETHANE |
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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 |
撮影 | 平均露光時間: 6.45 sec. / 電子線照射量: 49.6 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) |
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解析
ソフトウェア | 名称: PHENIX / バージョン: 1.12_2829: / 分類: 精密化 | ||||||||||||||||||||||||
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CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3次元再構成 | 解像度: 4.3 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 71057 / 対称性のタイプ: POINT | ||||||||||||||||||||||||
拘束条件 |
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