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基本情報
登録情報 | データベース: PDB / ID: 7l2e | ||||||
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タイトル | Cryo-EM structure of NTD-directed neutralizing antibody 4-18 in complex with prefusion SARS-CoV-2 spike glycoprotein | ||||||
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![]() | Viral Protein/IMMUNE SYSTEM / Neutralizing antibody / Fusion protein / Spike glycoprotein / COVID-19 / NTD / NTD-directed antibody / 4-18 / Viral protein / IMMUNE SYSTEM / 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: 2.97 Å | ||||||
![]() | Cerutti, G. / Shapiro, L. | ||||||
資金援助 | ![]()
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![]() | ![]() タイトル: Potent SARS-CoV-2 neutralizing antibodies directed against spike N-terminal domain target a single supersite. 著者: Gabriele Cerutti / Yicheng Guo / Tongqing Zhou / Jason Gorman / Myungjin Lee / Micah Rapp / Eswar R Reddem / Jian Yu / Fabiana Bahna / Jude Bimela / Yaoxing Huang / Phinikoula S Katsamba / ...著者: Gabriele Cerutti / Yicheng Guo / Tongqing Zhou / Jason Gorman / Myungjin Lee / Micah Rapp / Eswar R Reddem / Jian Yu / Fabiana Bahna / Jude Bimela / Yaoxing Huang / Phinikoula S Katsamba / Lihong Liu / Manoj S Nair / Reda Rawi / Adam S Olia / Pengfei Wang / Baoshan Zhang / Gwo-Yu Chuang / David D Ho / Zizhang Sheng / Peter D Kwong / Lawrence Shapiro / ![]() 要旨: Numerous antibodies that neutralize SARS-CoV-2 have been identified, and these generally target either the receptor-binding domain (RBD) or the N-terminal domain (NTD) of the viral spike. While RBD- ...Numerous antibodies that neutralize SARS-CoV-2 have been identified, and these generally target either the receptor-binding domain (RBD) or the N-terminal domain (NTD) of the viral spike. While RBD-directed antibodies have been extensively studied, far less is known about NTD-directed antibodies. Here, we report cryo-EM and crystal structures for seven potent NTD-directed neutralizing antibodies in complex with spike or isolated NTD. These structures defined several antibody classes, with at least one observed in multiple convalescent donors. The structures revealed that all seven antibodies target a common surface, bordered by glycans N17, N74, N122, and N149. This site-formed primarily by a mobile β-hairpin and several flexible loops-was highly electropositive, located at the periphery of the spike, and the largest glycan-free surface of NTD facing away from the viral membrane. Thus, in contrast to neutralizing RBD-directed antibodies that recognize multiple non-overlapping epitopes, potent NTD-directed neutralizing antibodies appear to target a single supersite. | ||||||
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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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PDBx/mmCIF形式 | ![]() | 723.5 KB | 表示 | ![]() |
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PDB形式 | ![]() | 609.9 KB | 表示 | ![]() |
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-検証レポート
文書・要旨 | ![]() | 2.9 MB | 表示 | ![]() |
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文書・詳細版 | ![]() | 2.9 MB | 表示 | |
XML形式データ | ![]() | 105.4 KB | 表示 | |
CIF形式データ | ![]() | 161.2 KB | 表示 | |
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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: 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: ![]() #2: 抗体 | 分子量: 24503.342 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: 23030.377 Da / 分子数: 3 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() #4: 多糖 | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose #5: 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: Prefusion SARS-CoV-2 spike glycoprotein in complex with 4-18 Fab タイプ: COMPLEX / Entity ID: #1-#3 / 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: 4.5 |
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: 42 e/Å2 フィルム・検出器のモデル: GATAN K3 BIOQUANTUM (6k x 4k) |
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解析
EMソフトウェア |
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CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||
対称性 | 点対称性: C3 (3回回転対称) | ||||||||||||||||||
3次元再構成 | 解像度: 2.97 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 280327 / 対称性のタイプ: POINT | ||||||||||||||||||
原子モデル構築 | プロトコル: FLEXIBLE FIT |