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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 | ||||||||||||
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![]() | TRANSLATION / translation initiation factor / viral protein | ||||||||||||
機能・相同性 | ![]() 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 | ||||||||||||
生物種 | ![]() ![]() | ||||||||||||
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 | ||||||||||||
![]() | Kashiwagi, K. / Ito, T. | ||||||||||||
資金援助 | ![]()
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![]() | ![]() 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. | ||||||||||||
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構造の表示
ムービー |
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構造ビューア | 分子: ![]() ![]() |
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PDBx/mmCIF形式 | ![]() | 879.5 KB | 表示 | ![]() |
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-検証レポート
文書・要旨 | ![]() | 828.3 KB | 表示 | ![]() |
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文書・詳細版 | ![]() | 873.3 KB | 表示 | |
XML形式データ | ![]() | 119.8 KB | 表示 | |
CIF形式データ | ![]() | 196.7 KB | 表示 | |
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-関連構造データ
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リンク
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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) ![]() ![]() ![]() #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) ![]() ![]() ![]() #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) ![]() ![]() ![]() #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) ![]() ![]() ![]() #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) ![]() ![]() ![]() |
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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) ![]() ![]() #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) ![]() ![]() |
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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) ![]() 遺伝子: NSS / 発現宿主: ![]() ![]() #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) ![]() ![]() |
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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 |
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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 |
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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: ![]() |
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) |
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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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