+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 6i2k | |||||||||
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タイトル | Structure of EV71 complexed with its receptor SCARB2 | |||||||||
要素 |
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キーワード | VIRUS / Enterovirus 71 / SCARB2 / Hand-foot-mouth disease / EV71 receptor | |||||||||
機能・相同性 | 機能・相同性情報 regulation of glucosylceramide catabolic process / regulation of carbohydrate catabolic process / regulation of endosome organization / aminophospholipid transport / regulation of lysosome organization / endosome to plasma membrane protein transport / scavenger receptor activity / protein targeting to lysosome / phosphatidylcholine binding / cargo receptor activity ...regulation of glucosylceramide catabolic process / regulation of carbohydrate catabolic process / regulation of endosome organization / aminophospholipid transport / regulation of lysosome organization / endosome to plasma membrane protein transport / scavenger receptor activity / protein targeting to lysosome / phosphatidylcholine binding / cargo receptor activity / cholesterol binding / phosphatidylserine binding / symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of RIG-I activity / symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of MDA-5 activity / symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of MAVS activity / picornain 2A / symbiont-mediated suppression of host mRNA export from nucleus / lysosomal lumen / receptor-mediated endocytosis / symbiont genome entry into host cell via pore formation in plasma membrane / picornain 3C / ribonucleoside triphosphate phosphatase activity / T=pseudo3 icosahedral viral capsid / host cell cytoplasmic vesicle membrane / sensory perception of sound / clathrin-coated endocytic vesicle membrane / positive regulation of neuron projection development / symbiont-mediated suppression of host gene expression / endocytic vesicle membrane / transmembrane signaling receptor activity / nucleoside-triphosphate phosphatase / channel activity / Cargo recognition for clathrin-mediated endocytosis / viral capsid / late endosome membrane / Clathrin-mediated endocytosis / protein-folding chaperone binding / virus receptor activity / monoatomic ion transmembrane transport / clathrin-dependent endocytosis of virus by host cell / host cell cytoplasm / DNA replication / entry receptor-mediated virion attachment to host cell / RNA helicase activity / endosome membrane / induction by virus of host autophagy / RNA-directed RNA polymerase / lysosomal membrane / Golgi membrane / viral RNA genome replication / cysteine-type endopeptidase activity / RNA-dependent RNA polymerase activity / focal adhesion / virus-mediated perturbation of host defense response / DNA-templated transcription / endoplasmic reticulum membrane / host cell nucleus / virion attachment to host cell / structural molecule activity / enzyme binding / protein homodimerization activity / proteolysis / RNA binding / extracellular exosome / ATP binding / membrane / metal ion binding / plasma membrane / cytoplasm 類似検索 - 分子機能 | |||||||||
生物種 | Homo sapiens (ヒト) Enterovirus A71 (エンテロウイルス) | |||||||||
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: 3.4 Å | |||||||||
データ登録者 | Zhou, D. / Zhao, Y. / Kotecha, A. / Fry, E.E. / Kelly, J. / Wang, X. / Rao, Z. / Rowlands, D.J. / Ren, J. / Stuart, D.I. | |||||||||
資金援助 | 英国, 1件
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引用 | ジャーナル: Nat Microbiol / 年: 2019 タイトル: Unexpected mode of engagement between enterovirus 71 and its receptor SCARB2. 著者: Daming Zhou / Yuguang Zhao / Abhay Kotecha / Elizabeth E Fry / James T Kelly / Xiangxi Wang / Zihe Rao / David J Rowlands / Jingshan Ren / David I Stuart / 要旨: Enterovirus 71 (EV71) is a common cause of hand, foot and mouth disease-a disease endemic especially in the Asia-Pacific region. Scavenger receptor class B member 2 (SCARB2) is the major receptor of ...Enterovirus 71 (EV71) is a common cause of hand, foot and mouth disease-a disease endemic especially in the Asia-Pacific region. Scavenger receptor class B member 2 (SCARB2) is the major receptor of EV71, as well as several other enteroviruses responsible for hand, foot and mouth disease, and plays a key role in cell entry. The isolated structures of EV71 and SCARB2 are known, but how they interact to initiate infection is not. Here, we report the EV71-SCARB2 complex structure determined at 3.4 Å resolution using cryo-electron microscopy. This reveals that SCARB2 binds EV71 on the southern rim of the canyon, rather than across the canyon, as predicted. Helices 152-163 (α5) and 183-193 (α7) of SCARB2 and the viral protein 1 (VP1) GH and VP2 EF loops of EV71 dominate the interaction, suggesting an allosteric mechanism by which receptor binding might facilitate the low-pH uncoating of the virus in the endosome/lysosome. Remarkably, many residues within the binding footprint are not conserved across SCARB2-dependent enteroviruses; however, a conserved proline and glycine seem to be key residues. Thus, although the virus maintains antigenic variability even within the receptor-binding footprint, the identification of binding 'hot spots' may facilitate the design of receptor mimic therapeutics less likely to quickly generate resistance. | |||||||||
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 | 6i2k.cif.gz | 232 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb6i2k.ent.gz | 188.8 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 6i2k.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 | 6i2k_validation.pdf.gz | 1.7 MB | 表示 | wwPDB検証レポート |
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文書・詳細版 | 6i2k_full_validation.pdf.gz | 1.7 MB | 表示 | |
XML形式データ | 6i2k_validation.xml.gz | 47.3 KB | 表示 | |
CIF形式データ | 6i2k_validation.cif.gz | 72.2 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/i2/6i2k ftp://data.pdbj.org/pub/pdb/validation_reports/i2/6i2k | 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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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 ABCDE
#1: タンパク質 | 分子量: 32755.766 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Enterovirus A71 (エンテロウイルス) / 参照: UniProt: Q66479*PLUS |
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#2: タンパク質 | 分子量: 27784.213 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Enterovirus A71 (エンテロウイルス) / 参照: UniProt: D4QGA2, UniProt: Q66479*PLUS |
#3: タンパク質 | 分子量: 26540.332 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Enterovirus A71 (エンテロウイルス) / 参照: UniProt: D4QGA3, UniProt: Q66479*PLUS |
#4: タンパク質 | 分子量: 6380.943 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Enterovirus A71 (エンテロウイルス) / 参照: UniProt: Q6YLE3, UniProt: Q66479*PLUS |
#5: タンパク質 | 分子量: 47727.750 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: SCARB2, CD36L2, LIMP2, LIMPII / 細胞株 (発現宿主): HEK293T / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: Q14108 |
-糖 , 6種, 8分子
#6: 多糖 | alpha-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1- ...alpha-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose | ||||||||
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#7: 多糖 | #8: 多糖 | beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta- ...beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose | #9: 多糖 | alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D- ...alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-6)]alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose | #10: 多糖 | alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2- ...alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose | #12: 糖 | |
-非ポリマー , 1種, 1分子
#11: 化合物 | ChemComp-906 / |
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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: Homo sapiens (ヒト) / 細胞: HEK293 | ||||||||||||||||||||||||
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: VIRION | ||||||||||||||||||||||||
天然宿主 | 生物種: Homo sapiens | ||||||||||||||||||||||||
緩衝液 | pH: 5.1 | ||||||||||||||||||||||||
試料 | 濃度: 0.6 mg/ml / 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES / 詳細: virus particle/SCARB2 ratio: 1:100 | ||||||||||||||||||||||||
急速凍結 | 凍結剤: ETHANE |
-電子顕微鏡撮影
実験機器 | モデル: Tecnai Polara / 画像提供: FEI Company |
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顕微鏡 | モデル: FEI POLARA 300 |
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 |
撮影 | 電子線照射量: 35 e/Å2 / 検出モード: SUPER-RESOLUTION フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) 実像数: 757 |
-解析
ソフトウェア | 名称: PHENIX / バージョン: 1.13_2998: / 分類: 精密化 | ||||||||||||||||||||||||||||
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EMソフトウェア |
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CTF補正 | タイプ: PHASE FLIPPING ONLY | ||||||||||||||||||||||||||||
対称性 | 点対称性: I (正20面体型対称) | ||||||||||||||||||||||||||||
3次元再構成 | 解像度: 3.4 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 10443 / クラス平均像の数: 4 / 対称性のタイプ: POINT | ||||||||||||||||||||||||||||
原子モデル構築 | B value: 150 / プロトコル: RIGID BODY FIT / 空間: REAL | ||||||||||||||||||||||||||||
原子モデル構築 |
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