+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 8zc1 | ||||||||||||
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タイトル | SARS-CoV-2 Omicron BA.2 spike trimer (6P) in complex with D1F6 Fab, focused refinement of RBD region | ||||||||||||
要素 |
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キーワード | VIRAL PROTEIN/IMMUNE SYSTEM / Spike protein / Antibody Fab fragment / Complex / VIRAL PROTEIN-IMMUNE SYSTEM complex | ||||||||||||
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 / 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 / symbiont-mediated suppression of host innate immune response / 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 | Severe acute respiratory syndrome coronavirus 2 (ウイルス) 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: 4.17 Å | ||||||||||||
データ登録者 | Liu, B. / Gao, X. / Li, Z. / Chen, Q. / He, J. / Xiong, X. | ||||||||||||
資金援助 | 3件
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引用 | ジャーナル: Cell Rep / 年: 2024 タイトル: An unconventional VH1-2 antibody tolerates escape mutations and shows an antigenic hotspot on SARS-CoV-2 spike. 著者: Banghui Liu / Xuefeng Niu / Yijun Deng / Zhaoyong Zhang / Yanqun Wang / Xijie Gao / Huan Liang / Zimu Li / Qian Wang / Yuanyi Cheng / Qiuluan Chen / Shuangshuang Huang / Yingxian Pan / ...著者: Banghui Liu / Xuefeng Niu / Yijun Deng / Zhaoyong Zhang / Yanqun Wang / Xijie Gao / Huan Liang / Zimu Li / Qian Wang / Yuanyi Cheng / Qiuluan Chen / Shuangshuang Huang / Yingxian Pan / Mengzhen Su / Xiancheng Lin / Chuanying Niu / Yinglin Chen / Wenyi Yang / Yudi Zhang / Qihong Yan / Jun He / Jincun Zhao / Ling Chen / Xiaoli Xiong / 要旨: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein continues to evolve antigenically, impacting antibody immunity. D1F6, an affinity-matured non-stereotypic VH1-2 ...The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein continues to evolve antigenically, impacting antibody immunity. D1F6, an affinity-matured non-stereotypic VH1-2 antibody isolated from a patient infected with the SARS-CoV-2 ancestral strain, effectively neutralizes most Omicron variants tested, including XBB.1.5. We identify that D1F6 in the immunoglobulin G (IgG) form is able to overcome the effect of most Omicron mutations through its avidity-enhanced multivalent S-trimer binding. Cryo-electron microscopy (cryo-EM) and biochemical analyses show that three simultaneous epitope mutations are generally needed to substantially disrupt the multivalent S-trimer binding by D1F6 IgG. Antigenic mutations at spike positions 346, 444, and 445, which appeared in the latest variants, have little effect on D1F6 binding individually. However, these mutations are able to act synergistically with earlier Omicron mutations to impair neutralization by affecting the interaction between D1F6 IgG and the S-trimer. These results provide insight into the mechanism by which accumulated antigenic mutations facilitate evasion of affinity-matured 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 | 8zc1.cif.gz | 114.3 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb8zc1.ent.gz | 86.7 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 8zc1.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/zc/8zc1 ftp://data.pdbj.org/pub/pdb/validation_reports/zc/8zc1 | HTTPS FTP |
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-関連構造データ
関連構造データ | 39919MC 8zbyC 8zbzC 8zc0C 8zc2C 8zc3C 8zc4C 8zc5C 8zc6C 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: 22153.029 Da / 分子数: 1 / 断片: RBD / 由来タイプ: 組換発現 由来: (組換発現) Severe acute respiratory syndrome coronavirus 2 (ウイルス) 株: Omicron/BA.2 / 遺伝子: S, 2 / 細胞株 (発現宿主): HEK293 / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: P0DTC2 |
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#2: 抗体 | 分子量: 23623.270 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 細胞株 (発現宿主): HEK293 / 発現宿主: Homo sapiens (ヒト) |
#3: 抗体 | 分子量: 24752.727 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 細胞株 (発現宿主): HEK293 / 発現宿主: Homo sapiens (ヒト) |
-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: SARS-CoV-2 Omicron BA.2 spike trimer (6P) in complex with D1F6 Fab, focused refinement of RBD region タイプ: COMPLEX / Entity ID: all / 由来: RECOMBINANT |
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由来(天然) | 生物種: Severe acute respiratory syndrome coronavirus 2 (ウイルス) |
由来(組換発現) | 生物種: Homo sapiens (ヒト) |
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 / 湿度: 100 % / 凍結前の試料温度: 295 K |
-電子顕微鏡撮影
実験機器 | モデル: Talos Arctica / 画像提供: FEI Company |
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顕微鏡 | モデル: FEI TALOS ARCTICA |
電子銃 | 電子線源: FIELD EMISSION GUN / 加速電圧: 200 kV / 照射モード: OTHER |
電子レンズ | モード: BRIGHT FIELD / 最大 デフォーカス(公称値): 2500 nm / 最小 デフォーカス(公称値): 800 nm |
撮影 | 電子線照射量: 60 e/Å2 / フィルム・検出器のモデル: GATAN K3 (6k x 4k) |
-解析
CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
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3次元再構成 | 解像度: 4.17 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 239007 / 対称性のタイプ: POINT | ||||||||||||||||||||||||
拘束条件 |
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