+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 7rq6 | ||||||
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タイトル | Cryo-EM structure of SARS-CoV-2 spike in complex with non-neutralizing NTD-directed CV3-13 Fab isolated from convalescent individual | ||||||
要素 |
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キーワード | VIRAL PROTEIN/IMMUNE SYSTEM (ウイルス性) / human non-neutralizing mAb / NTD-directed antibody / ADCC / novel NTD epitope / SARS-CoV-2 (SARSコロナウイルス2) / spike / N-terminal domain (N末端) / VIRAL PROTEIN-IMMUNE SYSTEM complex (ウイルス性) | ||||||
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 / 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 / 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) Homo sapiens (ヒト) | ||||||
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: 4.18 Å | ||||||
データ登録者 | Chen, Y. / Pozharski, E. / Tolbert, W.D. / Pazgier, M. | ||||||
資金援助 | 米国, 1件
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引用 | ジャーナル: Cell Rep / 年: 2022 タイトル: A Fc-enhanced NTD-binding non-neutralizing antibody delays virus spread and synergizes with a nAb to protect mice from lethal SARS-CoV-2 infection. 著者: Guillaume Beaudoin-Bussières / Yaozong Chen / Irfan Ullah / Jérémie Prévost / William D Tolbert / Kelly Symmes / Shilei Ding / Mehdi Benlarbi / Shang Yu Gong / Alexandra Tauzin / Romain ...著者: Guillaume Beaudoin-Bussières / Yaozong Chen / Irfan Ullah / Jérémie Prévost / William D Tolbert / Kelly Symmes / Shilei Ding / Mehdi Benlarbi / Shang Yu Gong / Alexandra Tauzin / Romain Gasser / Debashree Chatterjee / Dani Vézina / Guillaume Goyette / Jonathan Richard / Fei Zhou / Leonidas Stamatatos / Andrew T McGuire / Hughes Charest / Michel Roger / Edwin Pozharski / Priti Kumar / Walther Mothes / Pradeep D Uchil / Marzena Pazgier / Andrés Finzi / 要旨: Emerging evidence indicates that both neutralizing and Fc-mediated effector functions of antibodies contribute to protection against SARS-CoV-2. It is unclear whether Fc-effector functions alone can ...Emerging evidence indicates that both neutralizing and Fc-mediated effector functions of antibodies contribute to protection against SARS-CoV-2. It is unclear whether Fc-effector functions alone can protect against SARS-CoV-2. Here, we isolated CV3-13, a non-neutralizing antibody, from a convalescent individual with potent Fc-mediated effector functions. The cryoelectron microscopy structure of CV3-13 in complex with the SARS-CoV-2 spike reveals that the antibody binds from a distinct angle of approach to an N-terminal domain (NTD) epitope that only partially overlaps with the NTD supersite recognized by neutralizing antibodies. CV3-13 does not alter the replication dynamics of SARS-CoV-2 in K18-hACE2 mice, but its Fc-enhanced version significantly delays virus spread, neuroinvasion, and death in prophylactic settings. Interestingly, the combination of Fc-enhanced non-neutralizing CV3-13 with Fc-compromised neutralizing CV3-25 completely protects mice from lethal SARS-CoV-2 infection. Altogether, our data demonstrate that efficient Fc-mediated effector functions can potently contribute to the in vivo efficacy of anti-SARS-CoV-2 antibodies. | ||||||
履歴 |
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-構造の表示
構造ビューア | 分子: MolmilJmol/JSmol |
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-ダウンロードとリンク
-ダウンロード
PDBx/mmCIF形式 | 7rq6.cif.gz | 707.2 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb7rq6.ent.gz | 576.4 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 7rq6.json.gz | ツリー表示 | PDBx/mmJSON形式 | |
その他 | その他のダウンロード |
-検証レポート
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/rq/7rq6 ftp://data.pdbj.org/pub/pdb/validation_reports/rq/7rq6 | HTTPS FTP |
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-関連構造データ
関連構造データ | 24628MC 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 (文献) |
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類似構造データ | 類似検索 - 機能・相同性F&H 検索 |
-リンク
-集合体
登録構造単位 |
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-要素
#1: タンパク質 | 分子量: 138022.984 Da / 分子数: 3 / 変異: F817P, A892P, A899P, A942P, K986P, V987P / 由来タイプ: 組換発現 / 詳細: Prefusion-stabilized 由来: (組換発現) Severe acute respiratory syndrome coronavirus 2 (SARSコロナウイルス2) 遺伝子: S, 2 / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: P0DTC2 #2: 抗体 | 分子量: 24080.912 Da / 分子数: 3 / 由来タイプ: 天然 / 由来: (天然) Homo sapiens (ヒト) #3: 抗体 | 分子量: 23323.898 Da / 分子数: 3 / 由来タイプ: 天然 / 由来: (天然) Homo sapiens (ヒト) #4: 多糖 | #5: 糖 | ChemComp-NAG / 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 |
-試料調製
構成要素 | 名称: Cryo-EM structure of SARS-CoV-2 spike in complex with non-neutralizing, NTD-directed human antibody CV3-13 タイプ: COMPLEX / Entity ID: #1-#3 / 由来: MULTIPLE SOURCES | |||||||||||||||
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分子量 | 値: 0.67 MDa / 実験値: YES | |||||||||||||||
由来(天然) |
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由来(組換発現) | 生物種: Homo sapiens (ヒト) | |||||||||||||||
緩衝液 | pH: 8 | |||||||||||||||
緩衝液成分 |
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試料 | 濃度: 0.504 mg/ml / 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES 詳細: SARS-CoV-2 HexaPro spike (GnT1- produced) was incubated with 15-fold excess of CV3-13 Fab overnight at 4oC before purification on a Superose 6 300/10 GL column (GE Healthcare). The complex ...詳細: SARS-CoV-2 HexaPro spike (GnT1- produced) was incubated with 15-fold excess of CV3-13 Fab overnight at 4oC before purification on a Superose 6 300/10 GL column (GE Healthcare). The complex peak was harvested, concentrated to 0.50 mg/mL in the SEC buffer and immediately used for CryoEM grid preparation. | |||||||||||||||
試料支持 | グリッドの材料: COPPER / グリッドのサイズ: 200 divisions/in. / グリッドのタイプ: Quantifoil R1.2/1.3 | |||||||||||||||
急速凍結 | 装置: FEI VITROBOT MARK IV / 凍結剤: ETHANE / 湿度: 95 % / 凍結前の試料温度: 277 K |
-電子顕微鏡撮影
顕微鏡 | モデル: TFS GLACIOS |
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電子銃 | 電子線源: FIELD EMISSION GUN / 加速電圧: 200 kV / 照射モード: FLOOD BEAM |
電子レンズ | モード: BRIGHT FIELDBright-field microscopy |
試料ホルダ | 凍結剤: NITROGEN |
撮影 | 電子線照射量: 42.1531 e/Å2 フィルム・検出器のモデル: GATAN K3 BIOQUANTUM (6k x 4k) 実像数: 2181 |
-解析
EMソフトウェア |
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CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | |||||||||||||||||||||
粒子像の選択 | 選択した粒子像数: 916236 | |||||||||||||||||||||
対称性 | 点対称性: C3 (3回回転対称) | |||||||||||||||||||||
3次元再構成 | 解像度: 4.18 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 150882 / 対称性のタイプ: POINT | |||||||||||||||||||||
原子モデル構築 | プロトコル: FLEXIBLE FIT / 空間: REAL | |||||||||||||||||||||
原子モデル構築 |
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