+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 8t12 | ||||||
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タイトル | Cryo-EM structure of DENV2 NS5 in complex with human STAT2 with the N-terminal domain of STAT2 ordered. | ||||||
要素 |
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キーワード | IMMUNE SYSTEM/VIRAL PROTEIN / complex / IMMUNE SYSTEM-VIRAL PROTEIN complex | ||||||
機能・相同性 | 機能・相同性情報 ISGF3 complex / negative regulation of type I interferon-mediated signaling pathway / type I interferon-mediated signaling pathway / Interleukin-20 family signaling / regulation of mitochondrial fission / ubiquitin-like protein ligase binding / symbiont-mediated suppression of host JAK-STAT cascade via inhibition of host TYK2 activity / cell surface receptor signaling pathway via JAK-STAT / host cell mitochondrion / Regulation of IFNA/IFNB signaling ...ISGF3 complex / negative regulation of type I interferon-mediated signaling pathway / type I interferon-mediated signaling pathway / Interleukin-20 family signaling / regulation of mitochondrial fission / ubiquitin-like protein ligase binding / symbiont-mediated suppression of host JAK-STAT cascade via inhibition of host TYK2 activity / cell surface receptor signaling pathway via JAK-STAT / host cell mitochondrion / Regulation of IFNA/IFNB signaling / symbiont-mediated suppression of host JAK-STAT cascade via inhibition of STAT2 activity / symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of MAVS activity / ribonucleoside triphosphate phosphatase activity / channel activity / regulation of protein phosphorylation / Evasion by RSV of host interferon responses / response to peptide hormone / defense response / RNA polymerase II transcription regulator complex / monoatomic ion transmembrane transport / viral capsid / double-stranded RNA binding / Interferon alpha/beta signaling / regulation of cell population proliferation / clathrin-dependent endocytosis of virus by host cell / defense response to virus / mRNA (nucleoside-2'-O-)-methyltransferase activity / mRNA 5'-cap (guanine-N7-)-methyltransferase activity / Potential therapeutics for SARS / RNA helicase activity / protein dimerization activity / host cell endoplasmic reticulum membrane / DNA-binding transcription factor activity, RNA polymerase II-specific / symbiont-mediated suppression of host type I interferon-mediated signaling pathway / induction by virus of host autophagy / RNA polymerase II cis-regulatory region sequence-specific DNA binding / DNA-binding transcription factor activity / viral RNA genome replication / serine-type endopeptidase activity / RNA-dependent RNA polymerase activity / virus-mediated perturbation of host defense response / fusion of virus membrane with host endosome membrane / viral envelope / host cell nucleus / chromatin / regulation of transcription by RNA polymerase II / virion attachment to host cell / SARS-CoV-2 activates/modulates innate and adaptive immune responses / virion membrane / structural molecule activity / positive regulation of transcription by RNA polymerase II / proteolysis / extracellular region / nucleoplasm / ATP binding / identical protein binding / membrane / nucleus / metal ion binding / plasma membrane / cytosol / cytoplasm 類似検索 - 分子機能 | ||||||
生物種 | Homo sapiens (ヒト) Dengue virus type 2 (デング熱ウイルス) | ||||||
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: 3.34 Å | ||||||
データ登録者 | Biswal, M. / Lu, J. / Song, J. | ||||||
資金援助 | 米国, 1件
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引用 | ジャーナル: Commun Biol / 年: 2024 タイトル: A conformational selection mechanism of flavivirus NS5 for species-specific STAT2 inhibition. 著者: Mahamaya Biswal / Wangyuan Yao / Jiuwei Lu / Jianbin Chen / Juliet Morrison / Rong Hai / Jikui Song / 要旨: Flaviviruses, including Zika virus (ZIKV) and Dengue virus (DENV), rely on their non-structural protein 5 (NS5) for both replication of viral genome and suppression of host IFN signaling. DENV and ...Flaviviruses, including Zika virus (ZIKV) and Dengue virus (DENV), rely on their non-structural protein 5 (NS5) for both replication of viral genome and suppression of host IFN signaling. DENV and ZIKV NS5s were shown to facilitate proteosome-mediated protein degradation of human STAT2 (hSTAT2). However, how flavivirus NS5s have evolved for species-specific IFN-suppression remains unclear. Here we report structure-function characterization of the DENV serotype 2 (DENV2) NS5-hSTAT2 complex. The MTase and RdRP domains of DENV2 NS5 form an extended conformation to interact with the coiled-coil and N-terminal domains of hSTAT2, thereby promoting hSTAT2 degradation in cells. Disruption of the extended conformation of DENV2/ZIKV NS5, but not the alternative compact state, impaired their hSTAT2 binding. Our comparative structural analysis of flavivirus NS5s further reveals a conserved protein-interaction platform with subtle amino-acid variations likely underpinning diverse IFN-suppression mechanisms. Together, this study uncovers a conformational selection mechanism underlying species-specific hSTAT2 inhibition by flavivirus NS5. | ||||||
履歴 |
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-構造の表示
構造ビューア | 分子: MolmilJmol/JSmol |
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-ダウンロードとリンク
-ダウンロード
PDBx/mmCIF形式 | 8t12.cif.gz | 284.5 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb8t12.ent.gz | 222.3 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 8t12.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 | 8t12_validation.pdf.gz | 1.2 MB | 表示 | wwPDB検証レポート |
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文書・詳細版 | 8t12_full_validation.pdf.gz | 1.2 MB | 表示 | |
XML形式データ | 8t12_validation.xml.gz | 49.3 KB | 表示 | |
CIF形式データ | 8t12_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/t1/8t12 ftp://data.pdbj.org/pub/pdb/validation_reports/t1/8t12 | HTTPS FTP |
-関連構造データ
関連構造データ | 40952MC 8t13C M: このデータのモデリングに利用したマップデータ C: 同じ文献を引用 (文献) |
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類似構造データ | 類似検索 - 機能・相同性F&H 検索 |
-リンク
-集合体
登録構造単位 |
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1 |
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-要素
#1: タンパク質 | 分子量: 98025.031 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: STAT2 / 発現宿主: Escherichia coli BL21(DE3) (大腸菌) / 参照: UniProt: P52630 | ||
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#2: タンパク質 | 分子量: 103264.656 Da / 分子数: 1 / 由来タイプ: 組換発現 由来: (組換発現) Dengue virus type 2 (デング熱ウイルス) 発現宿主: Escherichia coli BL21(DE3) (大腸菌) / 参照: UniProt: Q91H74 | ||
#3: 化合物 | 研究の焦点であるリガンドがあるか | Y | |
-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: complex of DENV2 NS5 and huamn STAT2 / タイプ: COMPLEX / Entity ID: #1-#2 / 由来: MULTIPLE SOURCES | ||||||||||||
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由来(天然) |
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由来(組換発現) | 生物種: Escherichia coli BL21(DE3) (大腸菌) | ||||||||||||
緩衝液 | pH: 7.5 | ||||||||||||
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 FIELD / 最大 デフォーカス(公称値): 2000 nm / 最小 デフォーカス(公称値): 1000 nm |
撮影 | 電子線照射量: 50 e/Å2 / フィルム・検出器のモデル: GATAN K3 (6k x 4k) |
-解析
CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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3次元再構成 | 解像度: 3.34 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 99938 / 対称性のタイプ: POINT |