+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-6829 | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
タイトル | Cryo-EM Structure of CVA6 VLP | |||||||||
マップデータ | ||||||||||
試料 |
| |||||||||
キーワード | Coxsackievirus A6 / virus-like particle / cryo-EM / near-atomic resolution structure / epitope / VIRUS LIKE PARTICLE | |||||||||
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 / picornain 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 / viral capsid ...symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of MDA-5 activity / picornain 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 / viral capsid / nucleoside-triphosphate phosphatase / protein complex oligomerization / monoatomic ion channel activity / RNA helicase activity / symbiont entry into host cell / induction by virus of host autophagy / cysteine-type endopeptidase activity / RNA-directed RNA polymerase / viral RNA genome replication / virus-mediated perturbation of host defense response / RNA-dependent RNA polymerase activity / DNA-templated transcription / virion attachment to host cell / structural molecule activity / ATP hydrolysis activity / proteolysis / 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 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3.0 Å | |||||||||
データ登録者 | Chen J / Zhang C | |||||||||
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 |
|
-構造の表示
ムービー |
ムービービューア |
---|---|
構造ビューア | EMマップ: SurfViewMolmilJmol/JSmol |
添付画像 |
-ダウンロードとリンク
-EMDBアーカイブ
マップデータ | emd_6829.map.gz | 103.7 MB | EMDBマップデータ形式 | |
---|---|---|---|---|
ヘッダ (付随情報) | emd-6829-v30.xml emd-6829.xml | 11.6 KB 11.6 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_6829.png | 99.3 KB | ||
Filedesc metadata | emd-6829.cif.gz | 5.3 KB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-6829 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-6829 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_6829_validation.pdf.gz | 654.8 KB | 表示 | EMDB検証レポート |
---|---|---|---|---|
文書・詳細版 | emd_6829_full_validation.pdf.gz | 654.4 KB | 表示 | |
XML形式データ | emd_6829_validation.xml.gz | 8.1 KB | 表示 | |
CIF形式データ | emd_6829_validation.cif.gz | 9.2 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-6829 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-6829 | HTTPS FTP |
-関連構造データ
-リンク
EMDBのページ | EMDB (EBI/PDBe) / EMDataResource |
---|---|
「今月の分子」の関連する項目 |
-マップ
ファイル | ダウンロード / ファイル: emd_6829.map.gz / 形式: CCP4 / 大きさ: 421.9 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
ボクセルのサイズ | X=Y=Z: 0.82 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
密度 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
詳細 | EMDB XML:
CCP4マップ ヘッダ情報:
|
-添付データ
-試料の構成要素
-全体 : Coxsackievirus A6
全体 | 名称: Coxsackievirus A6 (コクサッキーウイルス) |
---|---|
要素 |
|
-超分子 #1: Coxsackievirus A6
超分子 | 名称: Coxsackievirus A6 / タイプ: virus / ID: 1 / 親要素: 0 / 含まれる分子: all / NCBI-ID: 86107 / 生物種: Coxsackievirus A6 / ウイルスタイプ: VIRUS-LIKE PARTICLE / ウイルス・単離状態: OTHER / ウイルス・エンベロープ: No / ウイルス・中空状態: Yes |
---|
-分子 #1: Capsid protein VP1
分子 | 名称: Capsid protein VP1 / タイプ: protein_or_peptide / ID: 1 / コピー数: 1 / 光学異性体: LEVO |
---|---|
由来(天然) | 生物種: Coxsackievirus A6 (コクサッキーウイルス) |
分子量 | 理論値: 33.644395 KDa |
組換発現 | 生物種: Spodoptera frugiperda (ツマジロクサヨトウ) |
配列 | 文字列: NDPISNAIEN AVSTLADTTI SRVTAANTAA SSHSLGTGRV PALQAAETGA SSNASDENLI ETRCVMNRNG VNEASVEHFY SRAGLVGVV EVKDSGTSQD GYTVWPIDVM GFVQQRRKLE LSTYMRFDAE FTFVSNLNDS TTPGMLLQYM YVPPGAPKPD G RKSYQWQT ...文字列: NDPISNAIEN AVSTLADTTI SRVTAANTAA SSHSLGTGRV PALQAAETGA SSNASDENLI ETRCVMNRNG VNEASVEHFY SRAGLVGVV EVKDSGTSQD GYTVWPIDVM GFVQQRRKLE LSTYMRFDAE FTFVSNLNDS TTPGMLLQYM YVPPGAPKPD G RKSYQWQT ATNPSIFAKL SDPPPQVSVP FMSPASAYQW FYDGYPTFGE HKQATNLQYG QCPNNMMGHF AIRTVSESTT GK NVHVRVY MRIKHVRAWV PRPFRSQAYM VKNYPTYSQT ISNTAADRAS ITTTDYEGGV PANPQRTF UniProtKB: Genome polyprotein |
-分子 #2: Capsid protein VP3
分子 | 名称: Capsid protein VP3 / タイプ: protein_or_peptide / ID: 2 / コピー数: 1 / 光学異性体: LEVO |
---|---|
由来(天然) | 生物種: Coxsackievirus A6 (コクサッキーウイルス) |
分子量 | 理論値: 26.375834 KDa |
組換発現 | 生物種: Spodoptera frugiperda (ツマジロクサヨトウ) |
配列 | 文字列: GLPTELKPGT NQFLTTDDGT SPPILPGFEP TPLIHIPGEF TSLLDLCRIE TILEVNNTTG TTGVNRLLIP VRAQNNVDQL CASFQVDPG RNGPWQSTMV GQICRYYTQW SGSLKVTFMF TGSFMATGKM LIAYTPPGSA QPTTREAAML GTHIVWDFGL Q SSVTLVIP ...文字列: GLPTELKPGT NQFLTTDDGT SPPILPGFEP TPLIHIPGEF TSLLDLCRIE TILEVNNTTG TTGVNRLLIP VRAQNNVDQL CASFQVDPG RNGPWQSTMV GQICRYYTQW SGSLKVTFMF TGSFMATGKM LIAYTPPGSA QPTTREAAML GTHIVWDFGL Q SSVTLVIP WISNTHFRAV KTGGVYDYYA TGIVTIWYQT NFVVPPDTPS EANIIALGAA QENFTLKLCK DTDEIRQTAE YQ UniProtKB: Genome polyprotein |
-分子 #3: capsid protein VP0
分子 | 名称: capsid protein VP0 / タイプ: protein_or_peptide / ID: 3 / コピー数: 1 / 光学異性体: LEVO |
---|---|
由来(天然) | 生物種: Coxsackievirus A6 (コクサッキーウイルス) |
分子量 | 理論値: 35.351426 KDa |
組換発現 | 生物種: Spodoptera frugiperda (ツマジロクサヨトウ) |
配列 | 文字列: MGAQVSAQKS GTHETGNIAT EGSTINFTNI NYYKDSYAAS ASRQDFTQDP TKFTSPVLDA IKEAAAPLQS PSVEACGYSD RVAQLTVGN STITTQEAAN IVLSYGEWPG YCPSTDATAV DKPTRPDVSV NRFYTLSTKS WKTESTGWYW KFPDVLNDTG V FGQNAQFH ...文字列: MGAQVSAQKS GTHETGNIAT EGSTINFTNI NYYKDSYAAS ASRQDFTQDP TKFTSPVLDA IKEAAAPLQS PSVEACGYSD RVAQLTVGN STITTQEAAN IVLSYGEWPG YCPSTDATAV DKPTRPDVSV NRFYTLSTKS WKTESTGWYW KFPDVLNDTG V FGQNAQFH YLYRSGFCMH VQCNASKFHQ GALLVVVIPE FVVAASSPAT KPNGQGLYPD FAHTNPGKEG QVFRDPYVLD AG IPLSQAL VFPHQWINLR TNNCATIIMP YVNALPFDSA LNHSNFGLAV IPISPLKYCN GATTEVPITL TIAPLNSEFS GLR QAIKQ UniProtKB: Genome polyprotein |
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
---|---|
解析 | 単粒子再構成法 |
試料の集合状態 | particle |
-試料調製
緩衝液 | pH: 7.2 |
---|---|
凍結 | 凍結剤: ETHANE |
-電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
---|---|
撮影 | フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) 平均電子線量: 42.0 e/Å2 |
電子線 | 加速電圧: 300 kV / 電子線源: FIELD EMISSION GUN |
電子光学系 | 照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELD |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |
-画像解析
初期モデル | モデルのタイプ: EMDB MAP |
---|---|
最終 再構成 | 解像度のタイプ: BY AUTHOR / 解像度: 3.0 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 使用した粒子像数: 11596 |
初期 角度割当 | タイプ: PROJECTION MATCHING |
最終 角度割当 | タイプ: PROJECTION MATCHING |