+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-30568 | |||||||||
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タイトル | eIF2B-eIF2(aP), aPg complex | |||||||||
マップデータ | ||||||||||
試料 |
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機能・相同性 | 機能・相同性情報 male germ cell proliferation / 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 ...male germ cell proliferation / 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 / formation of translation preinitiation complex / oligodendrocyte development / 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 / ABC-family proteins mediated transport / PKR-mediated signaling / response to peptide hormone / cytoplasmic stress granule / male gonad development / 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 / in utero embryonic development / cadherin binding / positive regulation of apoptotic process / GTPase activity / mRNA binding / synapse / GTP binding / mitochondrion / RNA binding / extracellular exosome / 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) | |||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 4.3 Å | |||||||||
データ登録者 | Kashiwagi K / Ito T | |||||||||
資金援助 | 日本, 2件
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引用 | ジャーナル: Mol Cell / 年: 2021 タイトル: ISRIB Blunts the Integrated Stress Response by Allosterically Antagonising the Inhibitory Effect of Phosphorylated eIF2 on eIF2B. 著者: Alisa F Zyryanova / Kazuhiro Kashiwagi / Claudia Rato / Heather P Harding / Ana Crespillo-Casado / Luke A Perera / Ayako Sakamoto / Madoka Nishimoto / Mayumi Yonemochi / Mikako Shirouzu / ...著者: Alisa F Zyryanova / Kazuhiro Kashiwagi / Claudia Rato / Heather P Harding / Ana Crespillo-Casado / Luke A Perera / Ayako Sakamoto / Madoka Nishimoto / Mayumi Yonemochi / Mikako Shirouzu / Takuhiro Ito / David Ron / 要旨: The small molecule ISRIB antagonizes the activation of the integrated stress response (ISR) by phosphorylated translation initiation factor 2, eIF2(αP). ISRIB and eIF2(αP) bind distinct sites in ...The small molecule ISRIB antagonizes the activation of the integrated stress response (ISR) by phosphorylated translation initiation factor 2, eIF2(αP). ISRIB and eIF2(αP) bind distinct sites in their common target, eIF2B, a guanine nucleotide exchange factor for eIF2. We have found that ISRIB-mediated acceleration of eIF2B's nucleotide exchange activity in vitro is observed preferentially in the presence of eIF2(αP) and is attenuated by mutations that desensitize eIF2B to the inhibitory effect of eIF2(αP). ISRIB's efficacy as an ISR inhibitor in cells also depends on presence of eIF2(αP). Cryoelectron microscopy (cryo-EM) showed that engagement of both eIF2B regulatory sites by two eIF2(αP) molecules remodels both the ISRIB-binding pocket and the pockets that would engage eIF2α during active nucleotide exchange, thereby discouraging both binding events. In vitro, eIF2(αP) and ISRIB reciprocally opposed each other's binding to eIF2B. These findings point to antagonistic allostery in ISRIB action on eIF2B, culminating in inhibition of the ISR. | |||||||||
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_30568.map.gz | 7.1 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-30568-v30.xml emd-30568.xml | 21.4 KB 21.4 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_30568.png | 54.7 KB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-30568 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-30568 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_30568_validation.pdf.gz | 328.5 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_30568_full_validation.pdf.gz | 328.1 KB | 表示 | |
XML形式データ | emd_30568_validation.xml.gz | 6.4 KB | 表示 | |
CIF形式データ | emd_30568_validation.cif.gz | 7.2 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-30568 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-30568 | 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_30568.map.gz / 形式: CCP4 / 大きさ: 103 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: 1.47 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 with eIF2(aP)
+超分子 #1: Complex of eIF2B with eIF2(aP)
+超分子 #2: eIF2B
+超分子 #3: eIF2(aP)
+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: Eukaryotic translation initiation factor 2 subunit 1
+分子 #7: Eukaryotic translation initiation factor 2 subunit 2
+分子 #8: 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 TECNAI ARCTICA |
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撮影 | フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) 平均電子線量: 50.0 e/Å2 |
電子線 | 加速電圧: 200 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: Talos Arctica / 画像提供: FEI Company |
-画像解析
最終 再構成 | 解像度のタイプ: BY AUTHOR / 解像度: 4.3 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 使用した粒子像数: 66721 |
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初期 角度割当 | タイプ: MAXIMUM LIKELIHOOD |
最終 角度割当 | タイプ: MAXIMUM LIKELIHOOD |