登録情報 データベース : EMDB / ID : EMD-31474 構造の表示 ダウンロードとリンクタイトル eIF2B-SFSV NSs-1-eIF2 マップデータ 詳細 試料複合体 : Complex of eIF2B, eIF2, and SFSV NSs複合体 : eIF2B, eIF2タンパク質・ペプチド : Translation initiation factor eIF-2B subunit alphaタンパク質・ペプチド : Translation initiation factor eIF-2B subunit betaタンパク質・ペプチド : Translation initiation factor eIF-2B subunit gammaタンパク質・ペプチド : Translation initiation factor eIF-2B subunit deltaタンパク質・ペプチド : Translation initiation factor eIF-2B subunit epsilonタンパク質・ペプチド : Eukaryotic translation initiation factor 2 subunit 1タンパク質・ペプチド : eIF2betaタンパク質・ペプチド : Eukaryotic translation initiation factor 2 subunit 3 残り4件を表示 表示を減らす複合体 : SFSV NSsタンパク質・ペプチド : Non-structural protein NS-S 詳細 キーワード translation initiation factor / viral protein / TRANSLATION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
regulation of translation in response to endoplasmic reticulum stress / translation initiation ternary complex / glial limiting end-foot / response to kainic acid / Cellular response to mitochondrial stress / response to manganese-induced endoplasmic reticulum stress / positive regulation of type B pancreatic cell apoptotic process / methionyl-initiator methionine tRNA binding / eukaryotic translation initiation factor 2B complex / 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 / response to kainic acid / Cellular response to mitochondrial stress / response to manganese-induced endoplasmic reticulum stress / positive regulation of type B pancreatic cell apoptotic process / methionyl-initiator methionine tRNA binding / eukaryotic translation initiation factor 2B complex / 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 / selenocysteine metabolic process / selenocysteine incorporation / protein-synthesizing GTPase / cytoplasmic translational initiation / translation factor activity, RNA binding / oligodendrocyte development / selenocysteine insertion sequence binding / formation of translation preinitiation complex / guanyl-nucleotide exchange factor complex / astrocyte development / eukaryotic 48S preinitiation complex / astrocyte differentiation / Formation of the ternary complex, and subsequently, the 43S complex / regulation of translational initiation / Translation initiation complex formation / Ribosomal scanning and start codon recognition / Response of EIF2AK4 (GCN2) to amino acid deficiency / L13a-mediated translational silencing of Ceruloplasmin expression / GTP hydrolysis and joining of the 60S ribosomal subunit / positive regulation of translational initiation / response to glucose / stress granule assembly / ovarian follicle development / translation initiation factor binding / translational initiation / translation initiation factor activity / cellular response to amino acid starvation / myelination / response to endoplasmic reticulum stress / guanyl-nucleotide exchange factor activity / central nervous system development / hippocampus development / ABC-family proteins mediated transport / PKR-mediated signaling / 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 / RNA binding / extracellular exosome / ATP binding / membrane / identical protein binding / nucleus / plasma membrane / cytoplasm / cytosol 類似検索 - 分子機能 Phlebovirus, non structural protein / Rift valley fever virus non structural protein-like / Rift valley fever virus non structural protein (NSs) like / 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 / Initiation factor 2B-related / Initiation factor 2B-like, C-terminal / Initiation factor 2 subunit family / eIF4-gamma/eIF5/eIF2-epsilon ... Phlebovirus, non structural protein / Rift valley fever virus non structural protein-like / Rift valley fever virus non structural protein (NSs) like / 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 / 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 / Translation elongation factor EF1A/initiation factor IF2gamma, C-terminal / Trimeric LpxA-like superfamily / S1 domain profile. / Translation elongation factor EFTu-like, domain 2 / Elongation factor Tu domain 2 / Ribosomal protein S1-like RNA-binding domain / 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 / Non-structural protein NS-S / 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) / 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 : 2.76 Å 詳細 データ登録者Kashiwagi K / Ito T 資金援助 日本, 3件 詳細 詳細を隠すOrganization Grant number 国 Japan Society for the Promotion of Science (JSPS) JP19H03172 日本 Japan Agency for Medical Research and Development (AMED) JP21gm1410001 日本 Japan Society for the Promotion of Science (JSPS) JP18K14644 日本
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 登録 2021年6月24日 - ヘッダ(付随情報) 公開 2021年12月1日 - マップ公開 2021年12月1日 - 更新 2024年6月12日 - 現状 2024年6月12日 処理サイト : PDBj / 状態 : 公開
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