登録情報 データベース : PDB / ID : 7d43 構造の表示 ダウンロードとリンクタイトル eIF2B-eIF2(aP), aPg complex 要素(Eukaryotic translation initiation factor 2 subunit ...) x 3 (Translation initiation factor eIF-2B subunit ...) x 5 詳細キーワード TRANSLATION / Complex / Translational control機能・相同性 機能・相同性情報分子機能 ドメイン・相同性 構成要素
male germ cell proliferation / regulation of translation in response to endoplasmic reticulum stress / translation initiation ternary complex / glial limiting end-foot / response to kainic acid / HRI-mediated signaling / 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 / response to kainic acid / HRI-mediated signaling / 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 / methionyl-initiator methionine tRNA binding / 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 / PERK regulates gene expression / eukaryotic translation initiation factor 2 complex / regulation of translational initiation in response to stress / protein-synthesizing GTPase / cytoplasmic translational initiation / translation factor activity, RNA binding / formation of translation preinitiation complex / oligodendrocyte development / guanyl-nucleotide exchange factor 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 / stress granule assembly / ovarian follicle development / translation initiation factor binding / myelination / translation initiation factor activity / cellular response to amino acid starvation / response to endoplasmic reticulum stress / guanyl-nucleotide exchange factor activity / central nervous system development / translational initiation / hippocampus development / PKR-mediated signaling / ABC-family proteins mediated transport / 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 oxidative stress / cellular response to heat / 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 Translation initiation factor eIF-2B subunit alpha, N-terminal / : / : / : / Translation initiation factor eIF-2B subunit epsilon, N-terminal / Translation initiation factor eIF-2B subunit epsilon, W2 domain / : / Translation initiation factor IF2/IF5 / Translation initiation factor IF2/IF5 domain / Translation initiation factor IF2/IF5, N-terminal ... Translation initiation factor eIF-2B subunit alpha, N-terminal / : / : / : / Translation initiation factor eIF-2B subunit epsilon, N-terminal / Translation initiation factor eIF-2B subunit epsilon, W2 domain / : / Translation initiation factor IF2/IF5 / Translation initiation factor IF2/IF5 domain / Translation initiation factor IF2/IF5, N-terminal / Translation initiation factor IF2/IF5, zinc-binding / Domain found in IF2B/IF5 / domain present in translation initiation factor eIF2B and eIF5 / Initiation factor 2B-related / Initiation factor 2B-like, C-terminal / Initiation factor 2 subunit family / eIF4-gamma/eIF5/eIF2-epsilon / Domain at the C-termini of GCD6, eIF-2B epsilon, eIF-4 gamma and eIF-5 / W2 domain / W2 domain profile. / IF2a, S1-like domain / Translation initiation factor 2, alpha subunit / Translation initiation factor 2, alpha subunit, middle domain superfamily / Translation initiation factor 2, alpha subunit, C-terminal / Eukaryotic translation initiation factor 2 alpha subunit / Initiation factor eIF2 gamma, domain 2 / Initiation factor eIF2 gamma, GTP-binding domain / Initiation factor eIF2 gamma, C-terminal / : / Initiation factor eIF2 gamma, C terminal / Nucleotidyl transferase domain / Nucleotidyl transferase / NagB/RpiA transferase-like / Bacterial transferase hexapeptide (six repeats) / Translation elongation factor EF1A/initiation factor IF2gamma, C-terminal / Trimeric LpxA-like superfamily / S1 domain profile. / Translation elongation factor EFTu-like, domain 2 / Ribosomal protein S1-like RNA-binding domain / Elongation factor Tu domain 2 / S1 RNA binding domain / S1 domain / Translational (tr)-type GTP-binding domain / Elongation factor Tu GTP binding domain / Translational (tr)-type guanine nucleotide-binding (G) domain profile. / Nucleotide-diphospho-sugar transferases / Armadillo-type fold / Translation protein, beta-barrel domain superfamily / Nucleic acid-binding, OB-fold / P-loop containing nucleoside triphosphate hydrolase 類似検索 - ドメイン・相同性 Eukaryotic translation initiation factor 2 subunit 1 / Eukaryotic translation initiation factor 2 subunit 2 / Eukaryotic translation initiation factor 2 subunit 3 / Translation initiation factor eIF2B subunit beta / Translation initiation factor eIF2B subunit epsilon / Translation initiation factor eIF2B subunit alpha / Translation initiation factor eIF2B subunit gamma / Translation initiation factor eIF2B subunit delta 類似検索 - 構成要素生物種 Homo sapiens (ヒト)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 : 4.3 Å 詳細データ登録者 Kashiwagi, K. / Ito, T. 資金援助 日本, 2件 詳細 詳細を隠す組織 認可番号 国 Japan Society for the Promotion of Science (JSPS) 日本 Japan Agency for Medical Research and Development (AMED) 日本
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 登録 2020年9月22日 登録サイト : PDBJ / 処理サイト : PDBJ改定 1.0 2020年12月9日 Provider : repository / タイプ : Initial release改定 1.1 2021年1月27日 Group : Database references / カテゴリ : citationItem : _citation.journal_volume / _citation.page_first / _citation.year
すべて表示 表示を減らす