+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 5yhq | ||||||
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タイトル | Cryo-EM Structure of CVA6 VLP | ||||||
要素 |
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キーワード | VIRUS LIKE PARTICLE (ウイルス様粒子) / Coxsackievirus A6 / virus-like particle (ウイルス様粒子) / cryo-EM (低温電子顕微鏡法) / near-atomic resolution structure / epitope (エピトープ) | ||||||
機能・相同性 | 機能・相同性情報 symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of MDA-5 activity / ピコルナイン2A / symbiont-mediated suppression of host mRNA export from nucleus / symbiont genome entry into host cell via pore formation in plasma membrane / picornain 3C / T=pseudo3 icosahedral viral capsid / host cell cytoplasmic vesicle membrane / cytoplasmic vesicle membrane / endocytosis involved in viral entry into host cell / カプシド ...symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of MDA-5 activity / ピコルナイン2A / symbiont-mediated suppression of host mRNA export from nucleus / symbiont genome entry into host cell via pore formation in plasma membrane / picornain 3C / T=pseudo3 icosahedral viral capsid / host cell cytoplasmic vesicle membrane / cytoplasmic vesicle membrane / endocytosis involved in viral entry into host cell / カプシド / : / nucleoside-triphosphate phosphatase / protein complex oligomerization / monoatomic ion channel activity / RNA helicase activity / induction by virus of host autophagy / symbiont entry into host cell / RNA依存性RNAポリメラーゼ / symbiont-mediated suppression of host gene expression / viral RNA genome replication / cysteine-type endopeptidase activity / RNA-dependent RNA polymerase activity / DNA-templated transcription / virion attachment to host cell / structural molecule activity / ATP hydrolysis activity / タンパク質分解 / RNA binding / ATP binding / metal ion binding 類似検索 - 分子機能 | ||||||
生物種 | Coxsackievirus A6 (コクサッキーウイルス) | ||||||
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 Å | ||||||
データ登録者 | Chen, J. / Zhang, C. / Huang, Z. / Cong, Y. | ||||||
引用 | ジャーナル: J Virol / 年: 2018 タイトル: A 3.0-Angstrom Resolution Cryo-Electron Microscopy Structure and Antigenic Sites of Coxsackievirus A6-Like Particles. 著者: Jinhuan Chen / Chao Zhang / Yu Zhou / Xiang Zhang / Chaoyun Shen / Xiaohua Ye / Wen Jiang / Zhong Huang / Yao Cong / 要旨: Coxsackievirus A6 (CVA6) has recently emerged as one of the predominant causative agents of hand, foot, and mouth disease (HFMD). The structure of the CVA6 mature viral particle has not been solved ...Coxsackievirus A6 (CVA6) has recently emerged as one of the predominant causative agents of hand, foot, and mouth disease (HFMD). The structure of the CVA6 mature viral particle has not been solved thus far. Our previous work shows that recombinant virus-like particles (VLPs) of CVA6 represent a promising CVA6 vaccine candidate. Here, we report the first cryo-electron microscopy (cryo-EM) structure of the CVA6 VLP at 3.0-Å resolution. The CVA6 VLP exhibits the characteristic features of enteroviruses but presents an open channel at the 2-fold axis and an empty, collapsed VP1 pocket, which is broadly similar to the structures of the enterovirus 71 (EV71) VLP and coxsackievirus A16 (CVA16) 135S expanded particle, indicating that the CVA6 VLP is in an expanded conformation. Structural comparisons reveal that two common salt bridges within protomers are maintained in the CVA6 VLP and other viruses of the genus, implying that these salt bridges may play a critical role in enteroviral protomer assembly. However, there are apparent structural differences among the CVA6 VLP, EV71 VLP, and CVA16 135S particle in the surface-exposed loops and C termini of subunit proteins, which are often antigenic sites for enteroviruses. By immunological assays, we identified two CVA6-specific linear B-cell epitopes (designated P42 and P59) located at the GH loop and the C-terminal region of VP1, respectively, in agreement with the structure-based prediction of antigenic sites. Our findings elucidate the structural basis and important antigenic sites of the CVA6 VLP as a strong vaccine candidate and also provide insight into enteroviral protomer assembly. Coxsackievirus A6 (CVA6) is becoming one of the major pathogens causing hand, foot, and mouth disease (HFMD), leading to significant morbidity and mortality in children and adults. However, no vaccine is currently available to prevent CVA6 infection. Our previous work shows that recombinant virus-like particles (VLPs) of CVA6 are a promising CVA6 vaccine candidate. Here, we present a 3.0-Å structure of the CVA6 VLP determined by cryo-electron microscopy. The overall architecture of the CVA6 VLP is similar to those of the expanded structures of enterovirus 71 (EV71) and coxsackievirus A16 (CVA16), but careful structural comparisons reveal significant differences in the surface-exposed loops and C termini of each capsid protein of these particles. In addition, we identified two CVA6-specific linear B-cell epitopes and mapped them to the GH loop and the C-terminal region of VP1, respectively. Collectively, our findings provide a structural basis and important antigenic information for CVA6 VLP vaccine development. | ||||||
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 | 5yhq.cif.gz | 138.2 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb5yhq.ent.gz | 105.3 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 5yhq.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/yh/5yhq ftp://data.pdbj.org/pub/pdb/validation_reports/yh/5yhq | 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
#1: タンパク質 | 分子量: 33644.395 Da / 分子数: 1 / 由来タイプ: 組換発現 由来: (組換発現) Coxsackievirus A6 (コクサッキーウイルス) 遺伝子: VP1 発現宿主: Spodoptera frugiperda (ツマジロクサヨトウ) 参照: UniProt: Q9YLP0 |
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#2: タンパク質 | 分子量: 26375.834 Da / 分子数: 1 / Fragment: UNP RESIDUES 326-565 / 由来タイプ: 組換発現 由来: (組換発現) Coxsackievirus A6 (コクサッキーウイルス) 発現宿主: Spodoptera frugiperda (ツマジロクサヨトウ) 参照: UniProt: Q6JKS2 |
#3: タンパク質 | 分子量: 35351.426 Da / 分子数: 1 / Fragment: UNP RESIDUES 1-325 / 由来タイプ: 組換発現 由来: (組換発現) Coxsackievirus A6 (コクサッキーウイルス) 発現宿主: Spodoptera frugiperda (ツマジロクサヨトウ) 参照: UniProt: Q6JKS2 |
-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: Coxsackievirus A6 / タイプ: VIRUS / Entity ID: all / 由来: RECOMBINANT |
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由来(天然) | 生物種: Coxsackievirus A6 (コクサッキーウイルス) |
由来(組換発現) | 生物種: Spodoptera frugiperda (ツマジロクサヨトウ) |
ウイルスについての詳細 | 中空か: YES / エンベロープを持つか: NO / 単離: OTHER / タイプ: VIRUS-LIKE PARTICLE |
緩衝液 | pH: 7.2 |
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: 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: FIELD EMISSION GUN / 加速電圧: 300 kV / 照射モード: FLOOD BEAM |
電子レンズ | モード: BRIGHT FIELDBright-field microscopy |
撮影 | 電子線照射量: 42 e/Å2 フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) |
-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 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 11596 / 対称性のタイプ: POINT | ||||||||||||||||||||||||
精密化 | 最高解像度: 3 Å | ||||||||||||||||||||||||
拘束条件 |
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