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基本情報
登録情報 | データベース: EMDB / ID: EMD-3880 | ||||||||||||
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タイトル | Coxsackievirus A24v in complex with the D1-D2 fragment of ICAM-1 | ||||||||||||
![]() | Coxsackievirus A24v in complex with the D1-D2 fragment of ICAM-1 | ||||||||||||
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![]() | Enterovirus / Receptor / Complex / picornavirus / VIRUS | ||||||||||||
機能・相同性 | ![]() regulation of leukocyte mediated cytotoxicity / T cell extravasation / positive regulation of cellular extravasation / regulation of ruffle assembly / T cell antigen processing and presentation / membrane to membrane docking / T cell activation via T cell receptor contact with antigen bound to MHC molecule on antigen presenting cell / adhesion of symbiont to host / establishment of endothelial barrier / heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules ...regulation of leukocyte mediated cytotoxicity / T cell extravasation / positive regulation of cellular extravasation / regulation of ruffle assembly / T cell antigen processing and presentation / membrane to membrane docking / T cell activation via T cell receptor contact with antigen bound to MHC molecule on antigen presenting cell / adhesion of symbiont to host / establishment of endothelial barrier / heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules / leukocyte migration / leukocyte cell-cell adhesion / cell adhesion mediated by integrin / Interleukin-10 signaling / symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of RIG-I activity / immunological synapse / Integrin cell surface interactions / negative regulation of endothelial cell apoptotic process / negative regulation of extrinsic apoptotic signaling pathway via death domain receptors / ribonucleoside triphosphate phosphatase activity / cellular response to leukemia inhibitory factor / picornain 2A / symbiont-mediated suppression of host mRNA export from nucleus / symbiont genome entry into host cell via pore formation in plasma membrane / cellular response to glucose stimulus / picornain 3C / T=pseudo3 icosahedral viral capsid / host cell cytoplasmic vesicle membrane / integrin binding / Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell / cellular response to amyloid-beta / Interferon gamma signaling / transmembrane signaling receptor activity / viral capsid / signaling receptor activity / host cell / nucleoside-triphosphate phosphatase / : / virus receptor activity / channel activity / monoatomic ion transmembrane transport / Interleukin-4 and Interleukin-13 signaling / receptor-mediated virion attachment to host cell / positive regulation of ERK1 and ERK2 cascade / RNA helicase activity / cell adhesion / membrane raft / endocytosis involved in viral entry into host cell / symbiont-mediated activation of host autophagy / RNA-directed RNA polymerase / external side of plasma membrane / cysteine-type endopeptidase activity / viral RNA genome replication / focal adhesion / RNA-directed RNA polymerase activity / DNA-templated transcription / symbiont entry into host cell / virion attachment to host cell / host cell nucleus / structural molecule activity / cell surface / proteolysis / extracellular space / RNA binding / extracellular exosome / zinc ion binding / ATP binding / membrane / plasma membrane 類似検索 - 分子機能 | ||||||||||||
生物種 | ![]() ![]() ![]() | ||||||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3.9 Å | ||||||||||||
![]() | Hurdiss DL / Ranson NA | ||||||||||||
資金援助 | ![]() ![]() ![]()
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![]() | ![]() タイトル: Role of enhanced receptor engagement in the evolution of a pandemic acute hemorrhagic conjunctivitis virus. 著者: Jim Baggen / Daniel L Hurdiss / Georg Zocher / Nitesh Mistry / Richard W Roberts / Jasper J Slager / Hongbo Guo / Arno L W van Vliet / Maryam Wahedi / Kimberley Benschop / Erwin Duizer / ...著者: Jim Baggen / Daniel L Hurdiss / Georg Zocher / Nitesh Mistry / Richard W Roberts / Jasper J Slager / Hongbo Guo / Arno L W van Vliet / Maryam Wahedi / Kimberley Benschop / Erwin Duizer / Cornelis A M de Haan / Erik de Vries / José M Casasnovas / Raoul J de Groot / Niklas Arnberg / Thilo Stehle / Neil A Ranson / Hendrik Jan Thibaut / Frank J M van Kuppeveld / ![]() ![]() ![]() ![]() ![]() 要旨: Acute hemorrhagic conjunctivitis (AHC) is a painful, contagious eye disease, with millions of cases in the last decades. Coxsackievirus A24 (CV-A24) was not originally associated with human disease, ...Acute hemorrhagic conjunctivitis (AHC) is a painful, contagious eye disease, with millions of cases in the last decades. Coxsackievirus A24 (CV-A24) was not originally associated with human disease, but in 1970 a pathogenic "variant" (CV-A24v) emerged, which is now the main cause of AHC. Initially, this variant circulated only in Southeast Asia, but it later spread worldwide, accounting for numerous AHC outbreaks and two pandemics. While both CV-A24 variant and nonvariant strains still circulate in humans, only variant strains cause AHC for reasons that are yet unknown. Since receptors are important determinants of viral tropism, we set out to map the CV-A24 receptor repertoire and establish whether changes in receptor preference have led to the increased pathogenicity and rapid spread of CV-A24v. Here, we identify ICAM-1 as an essential receptor for both AHC-causing and non-AHC strains. We provide a high-resolution cryo-EM structure of a virus-ICAM-1 complex, which revealed critical ICAM-1-binding residues. These data could help identify a possible conserved mode of receptor engagement among ICAM-1-binding enteroviruses and rhinoviruses. Moreover, we identify a single capsid substitution that has been adopted by all pandemic CV-A24v strains and we reveal that this adaptation enhances the capacity of CV-A24v to bind sialic acid. Our data elucidate the CV-A24v receptor repertoire and point to a role of enhanced receptor engagement in the adaptation to the eye, possibly enabling pandemic spread. | ||||||||||||
履歴 |
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構造の表示
ムービー |
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構造ビューア | EMマップ: ![]() ![]() ![]() |
添付画像 |
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マップデータ | ![]() | 219.1 MB | ![]() | |
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ヘッダ (付随情報) | ![]() ![]() | 19.5 KB 19.5 KB | 表示 表示 | ![]() |
FSC (解像度算出) | ![]() | 15.9 KB | 表示 | ![]() |
画像 | ![]() | 237.8 KB | ||
Filedesc metadata | ![]() | 6.8 KB | ||
その他 | ![]() | 302.3 MB | ||
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-検証レポート
文書・要旨 | ![]() | 596.5 KB | 表示 | ![]() |
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文書・詳細版 | ![]() | 596.1 KB | 表示 | |
XML形式データ | ![]() | 14.9 KB | 表示 | |
CIF形式データ | ![]() | 20.5 KB | 表示 | |
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-関連構造データ
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リンク
EMDBのページ | ![]() ![]() |
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「今月の分子」の関連する項目 |
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マップ
ファイル | ![]() | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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注釈 | Coxsackievirus A24v in complex with the D1-D2 fragment of ICAM-1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
投影像・断面図 | 画像のコントロール
画像は Spider により作成 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 1.0651 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
密度 |
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対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
詳細 | EMDB XML:
CCP4マップ ヘッダ情報:
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-添付データ
-追加マップ: Coxsackievirus A24v in complex with the D1-D2 fragment...
ファイル | emd_3880_additional.map | ||||||||||||
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注釈 | Coxsackievirus A24v in complex with the D1-D2 fragment of ICAM-1 (unsharpened map). | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
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試料の構成要素
-全体 : Coxsackievirus A24v in complex with the D1 and D2 domains of ICAM-1
全体 | 名称: Coxsackievirus A24v in complex with the D1 and D2 domains of ICAM-1 |
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要素 |
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-超分子 #1: Coxsackievirus A24v in complex with the D1 and D2 domains of ICAM-1
超分子 | 名称: Coxsackievirus A24v in complex with the D1 and D2 domains of ICAM-1 タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: all |
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分子量 | 理論値: 8 MDa |
-超分子 #2: Coxsackievirus A24
超分子 | 名称: Coxsackievirus A24 / タイプ: complex / ID: 2 / 親要素: 1 / 含まれる分子: #1-#3 |
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由来(天然) | 生物種: ![]() |
-超分子 #3: D1 and D2 domains of ICAM-1
超分子 | 名称: D1 and D2 domains of ICAM-1 / タイプ: complex / ID: 3 / 親要素: 1 / 含まれる分子: #4 |
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由来(天然) | 生物種: ![]() |
-分子 #1: VP1
分子 | 名称: VP1 / タイプ: protein_or_peptide / ID: 1 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() |
分子量 | 理論値: 34.378371 KDa |
配列 | 文字列: GIEETIDTVI TNALQLSQPK PQKQPTAQST PLTSGVNSQE VPALTAVETG ASGQAVPSDV IETRHVVNYK TRSESTLESF FGRSACVTI LEVENFNATT DADRKKQFTT WAITYTDTVQ LRRKLEFFTY SRFDLEMTFV ITERYYASNT GHARNQVYQL M YIPPGAPR ...文字列: GIEETIDTVI TNALQLSQPK PQKQPTAQST PLTSGVNSQE VPALTAVETG ASGQAVPSDV IETRHVVNYK TRSESTLESF FGRSACVTI LEVENFNATT DADRKKQFTT WAITYTDTVQ LRRKLEFFTY SRFDLEMTFV ITERYYASNT GHARNQVYQL M YIPPGAPR PTAWDDYTWQ SSSNPSVFYT YGSAPPRMSI PYVGIANAYS HFYDGFARVP LKDETVDSGD TYYGLVTIND FG TLAVRVV NEYNPARITS KIRVYMKPKH VRCWCPRPPR AVPYRGEGVD FKQDSITPLT AVENINTF UniProtKB: Genome polyprotein |
-分子 #2: VP2
分子 | 名称: VP2 / タイプ: protein_or_peptide / ID: 2 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() |
分子量 | 理論値: 29.817412 KDa |
配列 | 文字列: SPNVEACGYS DRVRQITLGN STITTQEAAN AVVAYGEWPS YLDDKEANPI DAPTEPDVSS NRFYTLDSVQ WKSTSRGWWW KLPDALKDM GMFGQNMYYH YLGRSGYTVH VQCNASKFHQ GALGVFAIPE YVMACNTEAK TSYVSYVNAN PGEKGGVFDN A YNPSAEAS ...文字列: SPNVEACGYS DRVRQITLGN STITTQEAAN AVVAYGEWPS YLDDKEANPI DAPTEPDVSS NRFYTLDSVQ WKSTSRGWWW KLPDALKDM GMFGQNMYYH YLGRSGYTVH VQCNASKFHQ GALGVFAIPE YVMACNTEAK TSYVSYVNAN PGEKGGVFDN A YNPSAEAS EGRKFAALDY LLGCGVLAGN AFVYPHQIIN LRTNNSATLV LPYVNSLAID CMAKHNNWGL VILPLCKLDY AP NSSTEIP ITVTIAPMFT EFNGLRNITV PATQ UniProtKB: Genome polyprotein |
-分子 #3: VP3
分子 | 名称: VP3 / タイプ: protein_or_peptide / ID: 3 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() |
分子量 | 理論値: 26.637746 KDa |
配列 | 文字列: GLPTMLTPGS SQFLTSDDFQ SPCALPNFDV TPPIHIPGEV FNMMELAEID SMIPMNSVTG KANTMEMYPI PLDDKGSATP IFSISLSPA SDKRLQYTML GEILNYYTHW TGSLRFTFLF CGSMMATGKI LLSYSPPGAK PPTTRKDAML GTHIIWDLGL Q SSCTMLAP ...文字列: GLPTMLTPGS SQFLTSDDFQ SPCALPNFDV TPPIHIPGEV FNMMELAEID SMIPMNSVTG KANTMEMYPI PLDDKGSATP IFSISLSPA SDKRLQYTML GEILNYYTHW TGSLRFTFLF CGSMMATGKI LLSYSPPGAK PPTTRKDAML GTHIIWDLGL Q SSCTMLAP WISNTVYRRC IKDDFTEGGY ITCFYQTRIV VPSGTPTSMF MLAFVSACPD FSVRLLRDTN HISQRTLFAR AQ UniProtKB: Genome polyprotein |
-分子 #4: Intercellular adhesion molecule 1
分子 | 名称: Intercellular adhesion molecule 1 / タイプ: protein_or_peptide / ID: 4 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() |
分子量 | 理論値: 9.2976 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: QTSVSPSKVI LPRGGSVLVT CSTSCDQPKL LGIETPLPKK ELLLPGNNRK VYELSNVQED SQPMCYSNCP DGQSTAKTFL TVYWT UniProtKB: Intercellular adhesion molecule 1 |
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
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![]() | 単粒子再構成法 |
試料の集合状態 | particle |
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試料調製
濃度 | 10 mg/mL |
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緩衝液 | pH: 7.5 詳細: TBS buffer (Coxsackievirus A24v) Phosphate buffer (ICAM-1 D1-D2) |
グリッド | モデル: Lacey grids coated in a 3 nm carbon film (Agar Scientific, UK) 材質: COPPER / メッシュ: 400 / 支持フィルム - 材質: CARBON / 支持フィルム - トポロジー: CONTINUOUS / 支持フィルム - Film thickness: 3 / 前処理 - タイプ: GLOW DISCHARGE |
凍結 | 凍結剤: ETHANE / チャンバー内湿度: 80 % / チャンバー内温度: 8 K / 装置: LEICA EM GP 詳細: On-grid binding of the receptor was performed by applying 3 microliters of ICAM-1 (9.85 mg/ml) to the pre-blotted, virus-containing grid, and leaving for 30 seconds before blotting and freezing. |
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電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
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撮影 | フィルム・検出器のモデル: FEI FALCON III (4k x 4k) 検出モード: INTEGRATING / 撮影したグリッド数: 1 / 実像数: 2652 / 平均露光時間: 1.5 sec. / 平均電子線量: 60.0 e/Å2 |
電子線 | 加速電圧: 300 kV / 電子線源: ![]() |
電子光学系 | 照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELD |
試料ステージ | 試料ホルダーモデル: FEI TITAN KRIOS AUTOGRID HOLDER ホルダー冷却材: NITROGEN |
実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |
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画像解析
-原子モデル構築 1
精密化 | 空間: REAL / プロトコル: OTHER |
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得られたモデル | ![]() PDB-6eit: |