+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 7eo0 | ||||||
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タイトル | FOOT AND MOUTH DISEASE VIRUS O/TIBET/99-BOUND THE SINGLE CHAIN FRAGMEN ANTIBODY C4 | ||||||
要素 |
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キーワード | VIRUS (ウイルス) / FOOT AND MOUTH DISEASE VIRUS (口蹄疫ウイルス) / FMDV (口蹄疫ウイルス) | ||||||
機能・相同性 | 機能・相同性情報 Immunoglobulin V-Type / Immunoglobulin V-set domain / Immunoglobulin V-set domain / Immunoglobulin subtype / 抗体 / Ig-like domain profile. / Immunoglobulin-like domain / Immunoglobulin-like domain superfamily / Immunoglobulin-like fold 類似検索 - ドメイン・相同性 | ||||||
生物種 | Bos taurus (ウシ) Foot-and-mouth disease virus (口蹄疫ウイルス) | ||||||
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: 3.75 Å | ||||||
データ登録者 | He, Y. / Li, K. | ||||||
引用 | ジャーナル: J Virol / 年: 2021 タイトル: Two Cross-Protective Antigen Sites on Foot-and-Mouth Disease Virus Serotype O Structurally Revealed by Broadly Neutralizing Antibodies from Cattle. 著者: Kun Li / Yong He / Li Wang / Pinghua Li / Sheng Wang / Pu Sun / Huifang Bao / Yimei Cao / Xuerong Liu / Guoqiang Zhu / Yali Song / Xingwen Bai / Xueqing Ma / Yuanfang Fu / Hong Yuan / Jing ...著者: Kun Li / Yong He / Li Wang / Pinghua Li / Sheng Wang / Pu Sun / Huifang Bao / Yimei Cao / Xuerong Liu / Guoqiang Zhu / Yali Song / Xingwen Bai / Xueqing Ma / Yuanfang Fu / Hong Yuan / Jing Zhang / Jian Wang / Yingli Chen / Dong Li / Zhiyong Lou / Zaixin Liu / Zengjun Lu / 要旨: Foot-and-mouth disease virus (FMDV) is a highly contagious virus that infects cloven-hoofed animals. Neutralizing antibodies play critical roles in antiviral infection. Although five known antigen ...Foot-and-mouth disease virus (FMDV) is a highly contagious virus that infects cloven-hoofed animals. Neutralizing antibodies play critical roles in antiviral infection. Although five known antigen sites that induce neutralizing antibodies have been defined, studies on cross-protective antigen sites are still scarce. We mapped two cross-protective antigen sites using 13 bovine-derived broadly neutralizing monoclonal antibodies (bnAbs) capable of neutralizing 4 lineages within 3 topotypes of FMDV serotype O. One antigen site was formed by a novel cluster of VP3-focused epitopes recognized by bnAb C4 and C4-like antibodies. The cryo-electron microscopy (cryo-EM) structure of the FMDV-OTi (O/Tibet/99)-C4 complex showed close contact with VP3 and a novel interprotomer antigen epitope around the icosahedral 3-fold axis of the FMDV particle, which is far beyond the known antigen site 4. The key determinants of the neutralizing function of C4 and C4-like antibodies on the capsid were βB (T65), the B-C loop (T68), the E-F loop (E131 and K134), and the H-I loop (G196), revealing a novel antigen site on VP3. The other antigen site comprised two group epitopes on VP2 recognized by 9 bnAbs (B57, B73, B77, B82, F28, F145, F150, E46, and E54), which belong to the known antigen site 2 of FMDV serotype O. Notably, bnAb C4 potently promoted FMDV RNA release in response to damage to viral particles, suggesting that the targeted epitope contains a trigger mechanism for particle disassembly. This study revealed two cross-protective antigen sites that can elicit cross-reactive neutralizing antibodies in cattle and provided new structural information for the design of a broad-spectrum molecular vaccine against FMDV serotype O. FMDV is the causative agent of foot-and-mouth disease (FMD), which is one of the most contagious and economically devastating diseases of domestic animals. The antigenic structure of FMDV serotype O is rather complicated, especially for those sites that can elicit a cross-protective neutralizing antibody response. Monoclonal neutralization antibodies provide both crucial defense components against FMDV infection and valuable tools for fine analysis of the antigenic structure. In this study, we found a cluster of novel VP3-focused epitopes using 13 bnAbs against FMDV serotype O from natural host cattle, which revealed two cross-protective antigen sites on VP2 and VP3. Antibody C4 targeting this novel epitope potently promoted viral particle disassembly and RNA release before infection, which may indicate a vulnerable region of FMDV. This study reveals new structural information about cross-protective antigen sites of FMDV serotype O, providing valuable and strong support for future research on broad-spectrum vaccines against FMD. | ||||||
履歴 |
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-構造の表示
ムービー |
ムービービューア |
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構造ビューア | 分子: MolmilJmol/JSmol |
-ダウンロードとリンク
-ダウンロード
PDBx/mmCIF形式 | 7eo0.cif.gz | 164.1 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb7eo0.ent.gz | 131.1 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 7eo0.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/eo/7eo0 ftp://data.pdbj.org/pub/pdb/validation_reports/eo/7eo0 | HTTPS FTP |
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-関連構造データ
-リンク
-集合体
登録構造単位 |
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対称性 | 点対称性: (シェーンフリース記号: I (正20面体型対称)) |
-要素
-タンパク質 , 5種, 5分子 1234H
#1: タンパク質 | 分子量: 23524.781 Da / 分子数: 1 / 由来タイプ: 天然 由来: (天然) Foot-and-mouth disease virus (口蹄疫ウイルス) |
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#2: タンパク質 | 分子量: 24338.387 Da / 分子数: 1 / 由来タイプ: 天然 由来: (天然) Foot-and-mouth disease virus (口蹄疫ウイルス) |
#3: タンパク質 | 分子量: 23875.801 Da / 分子数: 1 / 由来タイプ: 天然 由来: (天然) Foot-and-mouth disease virus (口蹄疫ウイルス) |
#4: タンパク質 | 分子量: 8778.129 Da / 分子数: 1 / 由来タイプ: 天然 由来: (天然) Foot-and-mouth disease virus (口蹄疫ウイルス) |
#5: タンパク質 | 分子量: 13914.535 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Bos taurus (ウシ) / 発現宿主: Escherichia coli BL21 (大腸菌) / 株 (発現宿主): BL21 / 参照: UniProt: A0A6B9SE04 |
-抗体 , 1種, 1分子 L
#6: 抗体 | 分子量: 12794.880 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Bos taurus (ウシ) / 発現宿主: Escherichia coli BL21 (大腸菌) / 株 (発現宿主): BL21 / 参照: UniProt: A0A6B9SCH7 |
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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 |
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由来(天然) |
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由来(組換発現) | 生物種: Escherichia coli BL21 (大腸菌) / 株: BL21 | ||||||||||||||||||||||||
緩衝液 | pH: 7.4 | ||||||||||||||||||||||||
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 |
-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: FLOOD BEAM |
電子レンズ | モード: OTHER |
撮影 | 電子線照射量: 50 e/Å2 フィルム・検出器のモデル: FEI FALCON II (4k x 4k) |
-解析
CTF補正 | タイプ: NONE |
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3次元再構成 | 解像度: 3.75 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 14458 / 対称性のタイプ: POINT |
精密化 | 最高解像度: 3.75 Å |