+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-31475 | ||||||||||||
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タイトル | eIF2B-SFSV NSs-2-eIF2 | ||||||||||||
マップデータ | |||||||||||||
試料 |
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キーワード | translation initiation factor / viral protein / TRANSLATION | ||||||||||||
機能・相同性 | 機能・相同性情報 regulation of translation in response to endoplasmic reticulum stress / translation initiation ternary complex / glial limiting end-foot / HRI-mediated signaling / response to kainic acid / Cellular response to mitochondrial stress / eukaryotic translation initiation factor 2B complex / response to manganese-induced endoplasmic reticulum stress / positive regulation of type B pancreatic cell apoptotic process / negative regulation of translational initiation in response to stress ...regulation of translation in response to endoplasmic reticulum stress / translation initiation ternary complex / glial limiting end-foot / HRI-mediated signaling / response to kainic acid / Cellular response to mitochondrial stress / eukaryotic translation initiation factor 2B complex / response to manganese-induced endoplasmic reticulum stress / positive regulation of type B pancreatic cell apoptotic process / negative regulation of translational initiation in response to stress / Response of EIF2AK1 (HRI) to heme deficiency / Recycling of eIF2:GDP / PERK-mediated unfolded protein response / methionyl-initiator methionine tRNA binding / PERK regulates gene expression / regulation of translational initiation in response to stress / eukaryotic translation initiation factor 2 complex / cytoplasmic translational initiation / translation factor activity, RNA binding / protein-synthesizing GTPase / guanyl-nucleotide exchange factor complex / oligodendrocyte development / formation of translation preinitiation complex / astrocyte development / eukaryotic 48S preinitiation complex / astrocyte differentiation / regulation of translational initiation / Formation of the ternary complex, and subsequently, the 43S complex / Ribosomal scanning and start codon recognition / Translation initiation complex formation / Response of EIF2AK4 (GCN2) to amino acid deficiency / mitophagy / GTP hydrolysis and joining of the 60S ribosomal subunit / L13a-mediated translational silencing of Ceruloplasmin expression / positive regulation of translational initiation / response to glucose / ovarian follicle development / stress granule assembly / translation initiation factor binding / response to endoplasmic reticulum stress / myelination / translation initiation factor activity / cellular response to amino acid starvation / guanyl-nucleotide exchange factor activity / hippocampus development / central nervous system development / translational initiation / PKR-mediated signaling / ABC-family proteins mediated transport / response to peptide hormone / cytoplasmic stress granule / cellular response to UV / ribosome binding / regulation of translation / T cell receptor signaling pathway / cellular response to heat / cellular response to oxidative stress / response to heat / cadherin binding / positive regulation of apoptotic process / GTPase activity / synapse / GTP binding / mitochondrion / RNA binding / extracellular exosome / ATP binding / identical protein binding / membrane / nucleus / plasma membrane / cytosol / cytoplasm 類似検索 - 分子機能 | ||||||||||||
生物種 | Homo sapiens (ヒト) / Sandfly fever sicilian virus (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: 3.59 Å | ||||||||||||
データ登録者 | Kashiwagi K / Ito T | ||||||||||||
資金援助 | 日本, 3件
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引用 | ジャーナル: Nat Commun / 年: 2021 タイトル: eIF2B-capturing viral protein NSs suppresses the integrated stress response. 著者: Kazuhiro Kashiwagi / Yuichi Shichino / Tatsuya Osaki / Ayako Sakamoto / Madoka Nishimoto / Mari Takahashi / Mari Mito / Friedemann Weber / Yoshiho Ikeuchi / Shintaro Iwasaki / Takuhiro Ito / 要旨: Various stressors such as viral infection lead to the suppression of cap-dependent translation and the activation of the integrated stress response (ISR), since the stress-induced phosphorylated ...Various stressors such as viral infection lead to the suppression of cap-dependent translation and the activation of the integrated stress response (ISR), since the stress-induced phosphorylated eukaryotic translation initiation factor 2 [eIF2(αP)] tightly binds to eIF2B to prevent it from exchanging guanine nucleotide molecules on its substrate, unphosphorylated eIF2. Sandfly fever Sicilian virus (SFSV) evades this cap-dependent translation suppression through the interaction between its nonstructural protein NSs and host eIF2B. However, its precise mechanism has remained unclear. Here, our cryo-electron microscopy (cryo-EM) analysis reveals that SFSV NSs binds to the α-subunit of eIF2B in a competitive manner with eIF2(αP). Together with SFSV NSs, eIF2B retains nucleotide exchange activity even in the presence of eIF2(αP), in line with the cryo-EM structures of the eIF2B•SFSV NSs•unphosphorylated eIF2 complex. A genome-wide ribosome profiling analysis clarified that SFSV NSs expressed in cultured human cells attenuates the ISR triggered by thapsigargin, an endoplasmic reticulum stress inducer. Furthermore, SFSV NSs introduced in rat hippocampal neurons and human induced-pluripotent stem (iPS) cell-derived motor neurons exhibits neuroprotective effects against the ISR-inducing stress. Since ISR inhibition is beneficial in various neurological disease models, SFSV NSs may be a promising therapeutic ISR inhibitor. | ||||||||||||
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 | 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_31475.map.gz | 208.1 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-31475-v30.xml emd-31475.xml | 22.7 KB 22.7 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_31475.png | 94.5 KB | ||
Filedesc metadata | emd-31475.cif.gz | 7.6 KB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-31475 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-31475 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_31475_validation.pdf.gz | 388.8 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_31475_full_validation.pdf.gz | 388.4 KB | 表示 | |
XML形式データ | emd_31475_validation.xml.gz | 7.7 KB | 表示 | |
CIF形式データ | emd_31475_validation.cif.gz | 8.8 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-31475 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-31475 | HTTPS FTP |
-関連構造データ
-リンク
EMDBのページ | EMDB (EBI/PDBe) / EMDataResource |
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「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_31475.map.gz / 形式: CCP4 / 大きさ: 347.6 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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: 0.829 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
-試料の構成要素
+全体 : Complex of eIF2B, eIF2, and SFSV NSs
+超分子 #1: Complex of eIF2B, eIF2, and SFSV NSs
+超分子 #2: eIF2B, eIF2
+超分子 #3: SFSV NSs
+分子 #1: Translation initiation factor eIF-2B subunit alpha
+分子 #2: Translation initiation factor eIF-2B subunit beta
+分子 #3: Translation initiation factor eIF-2B subunit gamma
+分子 #4: Translation initiation factor eIF-2B subunit delta
+分子 #5: Translation initiation factor eIF-2B subunit epsilon
+分子 #6: Non-structural protein NS-S
+分子 #7: Eukaryotic translation initiation factor 2 subunit 1
+分子 #8: eIF2beta
+分子 #9: Eukaryotic translation initiation factor 2 subunit 3
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
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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: 7.5 |
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凍結 | 凍結剤: ETHANE |
-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: GATAN K3 BIOQUANTUM (6k x 4k) 平均電子線量: 50.0 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 |
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最終 再構成 | 解像度のタイプ: BY AUTHOR / 解像度: 3.59 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 使用した粒子像数: 8106 |
初期 角度割当 | タイプ: MAXIMUM LIKELIHOOD |
最終 角度割当 | タイプ: MAXIMUM LIKELIHOOD |