+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 6eit | ||||||||||||
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タイトル | Coxsackievirus A24v in complex with the D1-D2 fragment of ICAM-1 | ||||||||||||
要素 |
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キーワード | VIRUS / Enterovirus / Receptor / Complex / picornavirus | ||||||||||||
機能・相同性 | 機能・相同性情報 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 / cell adhesion mediated by integrin / leukocyte cell-cell adhesion / leukocyte migration / Interleukin-10 signaling / immunological synapse / Integrin cell surface interactions / negative regulation of endothelial cell apoptotic process / negative regulation of extrinsic apoptotic signaling pathway via death domain receptors / 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 / ribonucleoside triphosphate phosphatase activity / T=pseudo3 icosahedral viral capsid / cellular response to leukemia inhibitory factor / cellular response to glucose stimulus / host cell cytoplasmic vesicle membrane / cytoplasmic vesicle membrane / endocytosis involved in viral entry into host cell / cellular response to amyloid-beta / Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell / Interferon gamma signaling / transmembrane signaling receptor activity / nucleoside-triphosphate phosphatase / integrin binding / channel activity / signaling receptor activity / virus receptor activity / monoatomic ion transmembrane transport / Interleukin-4 and Interleukin-13 signaling / collagen-containing extracellular matrix / RNA helicase activity / positive regulation of ERK1 and ERK2 cascade / receptor-mediated virion attachment to host cell / cell adhesion / symbiont-mediated suppression of host innate immune response / induction by virus of host autophagy / symbiont entry into host cell / membrane raft / RNA-directed RNA polymerase / viral RNA genome replication / external side of plasma membrane / cysteine-type endopeptidase activity / RNA-dependent RNA polymerase activity / focal adhesion / virus-mediated perturbation of host defense response / DNA-templated transcription / host cell nucleus / virion attachment to host cell / structural molecule activity / cell surface / proteolysis / RNA binding / extracellular space / extracellular exosome / ATP binding / membrane / metal ion binding / plasma membrane 類似検索 - 分子機能 | ||||||||||||
生物種 | Homo sapiens (ヒト) Coxsackievirus A24 (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: 3.9 Å | ||||||||||||
データ登録者 | Hurdiss, D.L. / Ranson, N.A. | ||||||||||||
資金援助 | オランダ, ドイツ, 英国, 3件
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引用 | ジャーナル: Proc Natl Acad Sci U S A / 年: 2018 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 |
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 | 6eit.cif.gz | 157.9 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb6eit.ent.gz | 128.5 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 6eit.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
文書・要旨 | 6eit_validation.pdf.gz | 833.2 KB | 表示 | wwPDB検証レポート |
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文書・詳細版 | 6eit_full_validation.pdf.gz | 838.3 KB | 表示 | |
XML形式データ | 6eit_validation.xml.gz | 35.7 KB | 表示 | |
CIF形式データ | 6eit_validation.cif.gz | 54.8 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/ei/6eit ftp://data.pdbj.org/pub/pdb/validation_reports/ei/6eit | HTTPS FTP |
-関連構造データ
-リンク
-集合体
登録構造単位 |
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1 |
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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: 34378.371 Da / 分子数: 1 / 由来タイプ: 天然 由来: (天然) Coxsackievirus A24 (コクサッキーウイルス) 細胞株: Normal human conjunctival (NHC) cells / 参照: UniProt: G3C8J7, UniProt: V9VEF3*PLUS |
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#2: タンパク質 | 分子量: 29817.412 Da / 分子数: 1 / 由来タイプ: 天然 由来: (天然) Coxsackievirus A24 (コクサッキーウイルス) 細胞株: Normal human conjunctival (NHC) cells / 参照: UniProt: A0A088F913, UniProt: V9VEF3*PLUS |
#3: タンパク質 | 分子量: 26637.746 Da / 分子数: 1 / 由来タイプ: 天然 由来: (天然) Coxsackievirus A24 (コクサッキーウイルス) 細胞株: Normal human conjunctival (NHC) cells / 参照: UniProt: Q0GYP7, UniProt: V9VEF3*PLUS |
#4: タンパク質 | 分子量: 9297.600 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: ICAM1 / 細胞株 (発現宿主): CHO Lec3.2.8.1 cells 発現宿主: Cricetulus griseus (モンゴルキヌゲネズミ) 参照: UniProt: P05362 |
-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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分子量 | 値: 8 MDa / 実験値: NO | ||||||||||||||||||||||||
由来(天然) |
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由来(組換発現) | 生物種: Cricetulus griseus (モンゴルキヌゲネズミ) | ||||||||||||||||||||||||
ウイルスについての詳細 | 中空か: NO / エンベロープを持つか: NO / 単離: STRAIN / タイプ: VIRION | ||||||||||||||||||||||||
天然宿主 | 生物種: Homo sapiens | ||||||||||||||||||||||||
ウイルス殻 | 直径: 300 nm / 三角数 (T数): 3 | ||||||||||||||||||||||||
緩衝液 | pH: 7.5 詳細: TBS buffer (Coxsackievirus A24v) Phosphate buffer (ICAM-1 D1-D2) | ||||||||||||||||||||||||
試料 | 濃度: 10 mg/ml / 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES | ||||||||||||||||||||||||
試料支持 | グリッドの材料: COPPER / グリッドのサイズ: 400 divisions/in. グリッドのタイプ: Lacey grids coated in a 3 nm carbon film (Agar Scientific, UK) | ||||||||||||||||||||||||
急速凍結 | 装置: LEICA EM GP / 凍結剤: ETHANE / 湿度: 80 % / 凍結前の試料温度: 8 K 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 |
-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 FIELD |
試料ホルダ | 凍結剤: NITROGEN 試料ホルダーモデル: FEI TITAN KRIOS AUTOGRID HOLDER |
撮影 | 平均露光時間: 1.5 sec. / 電子線照射量: 60 e/Å2 / 検出モード: INTEGRATING フィルム・検出器のモデル: FEI FALCON III (4k x 4k) 撮影したグリッド数: 1 / 実像数: 2652 |
-解析
EMソフトウェア | 名称: RELION / バージョン: 2 / カテゴリ: 3次元再構成 |
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CTF補正 | 詳細: gCTF / タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION |
対称性 | 点対称性: I (正20面体型対称) |
3次元再構成 | 解像度: 3.9 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 26311 / 対称性のタイプ: POINT |
原子モデル構築 | プロトコル: OTHER / 空間: REAL |