+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 7f67 | ||||||||||||
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タイトル | eIF2B-SFSV NSs-2-eIF2 | ||||||||||||
要素 |
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キーワード | TRANSLATION / translation initiation factor / viral protein | ||||||||||||
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 / central nervous system development / hippocampus development / translational initiation / 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 oxidative stress / cellular response to heat / 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 | 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: 3.59 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 | 分子: MolmilJmol/JSmol |
-ダウンロードとリンク
-ダウンロード
PDBx/mmCIF形式 | 7f67.cif.gz | 879.5 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb7f67.ent.gz | 695.1 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 7f67.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 | 7f67_validation.pdf.gz | 828.3 KB | 表示 | wwPDB検証レポート |
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文書・詳細版 | 7f67_full_validation.pdf.gz | 873.3 KB | 表示 | |
XML形式データ | 7f67_validation.xml.gz | 119.8 KB | 表示 | |
CIF形式データ | 7f67_validation.cif.gz | 196.7 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/f6/7f67 ftp://data.pdbj.org/pub/pdb/validation_reports/f6/7f67 | HTTPS FTP |
-関連構造データ
-リンク
-集合体
登録構造単位 |
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-要素
-Translation initiation factor eIF-2B subunit ... , 5種, 10分子 ABCDEFGHIJ
#1: タンパク質 | 分子量: 33754.148 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: EIF2B1, EIF2BA / 発現宿主: Escherichia coli (大腸菌) / 参照: UniProt: Q14232 #2: タンパク質 | 分子量: 39039.547 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: EIF2B2, EIF2BB / 発現宿主: Escherichia coli (大腸菌) / 参照: UniProt: P49770 #3: タンパク質 | 分子量: 50304.230 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: EIF2B3 / 発現宿主: Escherichia coli (大腸菌) / 参照: UniProt: Q9NR50 #4: タンパク質 | 分子量: 57640.168 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: EIF2B4, EIF2BD / 発現宿主: Escherichia coli (大腸菌) / 参照: UniProt: Q9UI10 #5: タンパク質 | 分子量: 80466.609 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: EIF2B5, EIF2BE / 発現宿主: Escherichia coli (大腸菌) / 参照: UniProt: Q13144 |
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-Eukaryotic translation initiation factor 2 subunit ... , 2種, 4分子 NQST
#7: タンパク質 | 分子量: 36161.180 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: EIF2S1, EIF2A / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: P05198 #9: タンパク質 | 分子量: 51178.406 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: EIF2S3, EIF2G / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: P41091, protein-synthesizing GTPase |
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-タンパク質 / タンパク質・ペプチド , 2種, 4分子 KLOR
#6: タンパク質 | 分子量: 29695.385 Da / 分子数: 2 / 由来タイプ: 組換発現 由来: (組換発現) Sandfly fever sicilian virus (ウイルス) 遺伝子: NSS / 発現宿主: Escherichia coli (大腸菌) / 参照: UniProt: P12792 #8: タンパク質・ペプチド | 分子量: 1209.482 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 発現宿主: Homo sapiens (ヒト) |
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-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 |
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由来(天然) |
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由来(組換発現) |
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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 |
撮影 | 電子線照射量: 50 e/Å2 フィルム・検出器のモデル: GATAN K3 BIOQUANTUM (6k x 4k) |
-解析
ソフトウェア | 名称: PHENIX / バージョン: 1.19.2_4158: / 分類: 精密化 | ||||||||||||||||||||||||
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CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3次元再構成 | 解像度: 3.59 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 8106 / 対称性のタイプ: POINT | ||||||||||||||||||||||||
拘束条件 |
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