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基本情報
登録情報 | データベース: PDB / ID: 7cab | ||||||
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タイトル | Structural basis for neutralization of SARS-CoV-2 and SARS-CoV by a potent therapeutic antibody | ||||||
![]() | Spike glycoprotein | ||||||
![]() | VIRAL PROTEIN / SARS-CoV-2 / Spike glycoprotein | ||||||
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 / Attachment and Entry / membrane fusion / symbiont-mediated suppression of host innate immune response / 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: 3.52 Å | ||||||
![]() | Zhe, L. / Cao, L. / Deng, Y. / Sun, Y. / Wang, N. / Xie, L. / Wang, Y. / Rao, Z. / Qin, C. / Wang, X. | ||||||
![]() | ![]() タイトル: Structural basis for neutralization of SARS-CoV-2 and SARS-CoV by a potent therapeutic antibody. 著者: Zhe Lv / Yong-Qiang Deng / Qing Ye / Lei Cao / Chun-Yun Sun / Changfa Fan / Weijin Huang / Shihui Sun / Yao Sun / Ling Zhu / Qi Chen / Nan Wang / Jianhui Nie / Zhen Cui / Dandan Zhu / Neil ...著者: Zhe Lv / Yong-Qiang Deng / Qing Ye / Lei Cao / Chun-Yun Sun / Changfa Fan / Weijin Huang / Shihui Sun / Yao Sun / Ling Zhu / Qi Chen / Nan Wang / Jianhui Nie / Zhen Cui / Dandan Zhu / Neil Shaw / Xiao-Feng Li / Qianqian Li / Liangzhi Xie / Youchun Wang / Zihe Rao / Cheng-Feng Qin / Xiangxi Wang / ![]() 要旨: The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in an unprecedented public health crisis. There are no approved ...The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in an unprecedented public health crisis. There are no approved vaccines or therapeutics for treating COVID-19. Here we report a humanized monoclonal antibody, H014, that efficiently neutralizes SARS-CoV-2 and SARS-CoV pseudoviruses as well as authentic SARS-CoV-2 at nanomolar concentrations by engaging the spike (S) receptor binding domain (RBD). H014 administration reduced SARS-CoV-2 titers in infected lungs and prevented pulmonary pathology in a human angiotensin-converting enzyme 2 mouse model. Cryo-electron microscopy characterization of the SARS-CoV-2 S trimer in complex with the H014 Fab fragment unveiled a previously uncharacterized conformational epitope, which was only accessible when the RBD was in an open conformation. Biochemical, cellular, virological, and structural studies demonstrated that H014 prevents attachment of SARS-CoV-2 to its host cell receptors. Epitope analysis of available neutralizing antibodies against SARS-CoV and SARS-CoV-2 uncovered broad cross-protective epitopes. Our results highlight a key role for antibody-based therapeutic interventions in the treatment of COVID-19. | ||||||
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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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PDBx/mmCIF形式 | ![]() | 602.3 KB | 表示 | ![]() |
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PDB形式 | ![]() | 505.3 KB | 表示 | ![]() |
PDBx/mmJSON形式 | ![]() | ツリー表示 | ![]() | |
その他 | ![]() |
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アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
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-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
#1: タンパク質 | 分子量: 133945.516 Da / 分子数: 3 / 断片: UNP residues 1-1208 変異: R682G, R683S, R685S, K835M, T844M, A846Y, D848A, L849M, I850Q, C851M, Q853Y, K854R K986P, V987P 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): HEK293T / 発現宿主: ![]() #2: 多糖 | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose #3: 糖 | ChemComp-NAG / 研究の焦点であるリガンドがあるか | Y | |
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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 trimer / タイプ: COMPLEX / Entity ID: #1 / 由来: RECOMBINANT |
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由来(天然) | 生物種: ![]() ![]() |
由来(組換発現) | 生物種: ![]() |
緩衝液 | pH: 8 |
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 |
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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 | 電子線照射量: 60 e/Å2 / 検出モード: SUPER-RESOLUTION フィルム・検出器のモデル: GATAN K2 QUANTUM (4k x 4k) |
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解析
ソフトウェア | 名称: PHENIX / バージョン: 1.10.1_2155: / 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: 3.52 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 273158 / 対称性のタイプ: POINT | ||||||||||||||||||||||||
拘束条件 |
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