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データを開く
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基本情報
| 登録情報 | ![]() | |||||||||
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| タイトル | Viral protein DP71L in complex with phosphorylated eIF2alpha (NTD) and protein phosphatase 1A (D64A), stabilized by G-actin/DNAseI | |||||||||
マップデータ | ||||||||||
試料 |
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キーワード | Phosphatase / complex / ISR / TRANSLATION | |||||||||
| 機能・相同性 | 機能・相同性情報regulation of neutrophil mediated cytotoxicity / zymogen granule / regulation of macromolecule metabolic process / regulation of acute inflammatory response / regulation of glycogen catabolic process / protein serine/threonine phosphatase inhibitor activity / positive regulation of termination of RNA polymerase II transcription, poly(A)-coupled / translation initiation ternary complex / regulation of translation in response to endoplasmic reticulum stress / regulation of primary metabolic process ...regulation of neutrophil mediated cytotoxicity / zymogen granule / regulation of macromolecule metabolic process / regulation of acute inflammatory response / regulation of glycogen catabolic process / protein serine/threonine phosphatase inhibitor activity / positive regulation of termination of RNA polymerase II transcription, poly(A)-coupled / translation initiation ternary complex / regulation of translation in response to endoplasmic reticulum stress / regulation of primary metabolic process / glial limiting end-foot / HRI-mediated signaling / response to manganese-induced endoplasmic reticulum stress / deoxyribonuclease I / PTW/PP1 phosphatase complex / Cellular response to mitochondrial stress / positive regulation of type B pancreatic cell apoptotic process / Response of EIF2AK1 (HRI) to heme deficiency / Recycling of eIF2:GDP / negative regulation of translational initiation in response to stress / protein phosphatase type 1 complex / PERK-mediated unfolded protein response / PERK regulates gene expression / glycogen granule / RNA polymerase II promoter clearance / response to kainic acid / RNA polymerase II CTD heptapeptide repeat S5 phosphatase activity / eukaryotic translation initiation factor 2 complex / symbiont-mediated suppression of host translation initiation / neutrophil activation involved in immune response / cadherin binding involved in cell-cell adhesion / deoxyribonuclease I activity / protein phosphatase 1 binding / regulation of translational initiation in response to stress / eukaryotic 48S preinitiation complex / positive regulation of extrinsic apoptotic signaling pathway in absence of ligand / DNA catabolic process / regulation of canonical Wnt signaling pathway / protein dephosphorylation / cytoskeletal motor activator activity / Phosphorylation and nuclear translocation of the CRY:PER:kinase complex / glycogen metabolic process / protein-serine/threonine phosphatase / branching morphogenesis of an epithelial tube / Triglyceride catabolism / myosin heavy chain binding / entrainment of circadian clock by photoperiod / Formation of the ternary complex, and subsequently, the 43S complex / tropomyosin binding / actin filament bundle / troponin I binding / protein serine/threonine phosphatase activity / Ribosomal scanning and start codon recognition / filamentous actin / mesenchyme migration / Translation initiation complex formation / telomere maintenance in response to DNA damage / phosphatase activity / Maturation of hRSV A proteins / negative regulation of transcription elongation by RNA polymerase II / skeletal muscle myofibril / actin filament bundle assembly / transition metal ion binding / striated muscle thin filament / skeletal muscle thin filament assembly / actin monomer binding / DARPP-32 events / positive regulation of glycogen biosynthetic process / Response of EIF2AK4 (GCN2) to amino acid deficiency / ribonucleoprotein complex binding / GTP hydrolysis and joining of the 60S ribosomal subunit / L13a-mediated translational silencing of Ceruloplasmin expression / mitophagy / skeletal muscle fiber development / stress fiber / titin binding / phosphoprotein phosphatase activity / actin filament polymerization / translation initiation factor activity / lung development / response to endoplasmic reticulum stress / cellular response to amino acid starvation / stress granule assembly / Downregulation of TGF-beta receptor signaling / filopodium / actin filament / adherens junction / circadian regulation of gene expression / positive regulation of transcription elongation by RNA polymerase II / centriole / sperm end piece / translational initiation / regulation of circadian rhythm / PKR-mediated signaling / response to lead ion / ABC-family protein mediated transport / 加水分解酵素; 酸無水物に作用; 酸無水物に作用・細胞または細胞小器官の運動に関与 / cytoplasmic stress granule / calcium-dependent protein binding / cellular response to UV 類似検索 - 分子機能 | |||||||||
| 生物種 | Homo sapiens (ヒト) / ![]() African swine fever virus (アフリカ豚コレラウイルス) / ![]() ![]() | |||||||||
| 手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3.03 Å | |||||||||
データ登録者 | Reineke LC / Dalwadi U / Croll T / Arthur C / Lee DJ / Frost A / Costa-Mattioli M | |||||||||
| 資金援助 | 1件
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引用 | ジャーナル: bioRxiv / 年: 2025タイトル: Harnessing the Evolution of Proteostasis Networks to Reverse Cognitive Dysfunction. 要旨: The integrated stress response (ISR) is a highly conserved network essential for maintaining cellular homeostasis and cognitive function. Here, we investigated how persistent ISR activation impacts ...The integrated stress response (ISR) is a highly conserved network essential for maintaining cellular homeostasis and cognitive function. Here, we investigated how persistent ISR activation impacts cognitive performance, primarily focusing on a PPP1R15B genetic variant associated with intellectual disability. By generating a novel mouse model that mimics this human condition, we revealed that this variant destabilizes the PPP1R15B•PP1 phosphatase complex, resulting in chronic ISR activation, impaired protein synthesis, and deficits in long-term memory. Importantly, we found that the cognitive and synaptic deficits in mice are directly due to ISR activation. Leveraging insights from evolutionary biology, we characterized DP71L, a viral orthologue of PPP1R15B, through detailed molecular and structural analyses, uncovering its mechanism of action as a potent pan-ISR inhibitor. Remarkably, we found that DP71L not only buffers cognitive decline associated with a wide array of conditions-including Down syndrome, Alzheimer's disease and aging-but also enhances long-term synaptic plasticity and memory in healthy mice. These findings highlight the promise of utilizing evolutionary insight to inform innovative therapeutic strategies. | |||||||||
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構造の表示
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ダウンロードとリンク
-EMDBアーカイブ
| マップデータ | emd_49223.map.gz | 58.3 MB | EMDBマップデータ形式 | |
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| ヘッダ (付随情報) | emd-49223-v30.xml emd-49223.xml | 23.5 KB 23.5 KB | 表示 表示 | EMDBヘッダ |
| 画像 | emd_49223.png | 132.7 KB | ||
| Filedesc metadata | emd-49223.cif.gz | 8 KB | ||
| アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-49223 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-49223 | HTTPS FTP |
-関連構造データ
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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 |
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マップ
| ファイル | ダウンロード / ファイル: emd_49223.map.gz / 形式: CCP4 / 大きさ: 125 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: 0.9286 Å | ||||||||||||||||||||||||||||||||||||
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| 対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||
| 詳細 | EMDB XML:
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-添付データ
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試料の構成要素
-全体 : PP1A holo-phosphatase complex with viral protein DP71L, G-actin, ...
| 全体 | 名称: PP1A holo-phosphatase complex with viral protein DP71L, G-actin, DNAseI, and substrate phospho-eIF2alpha (2-187) |
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| 要素 |
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-超分子 #1: PP1A holo-phosphatase complex with viral protein DP71L, G-actin, ...
| 超分子 | 名称: PP1A holo-phosphatase complex with viral protein DP71L, G-actin, DNAseI, and substrate phospho-eIF2alpha (2-187) タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1-#5 |
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| 由来(天然) | 生物種: Homo sapiens (ヒト) |
| 分子量 | 理論値: 140 KDa |
-分子 #1: Protein DP71L
| 分子 | 名称: Protein DP71L / タイプ: protein_or_peptide / ID: 1 / コピー数: 1 / 光学異性体: LEVO |
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| 由来(天然) | 生物種: ![]() African swine fever virus (アフリカ豚コレラウイルス) |
| 分子量 | 理論値: 8.43573 KDa |
| 組換発現 | 生物種: ![]() |
| 配列 | 文字列: MGGRRRKKRT NDVKHVRFAA AVEVWEADDI ERKGPWEQAA VDRFRFQRRI ASVEELLSAV LLRQKKLLEQ Q UniProtKB: Protein DP71L |
-分子 #2: Serine/threonine-protein phosphatase PP1-alpha catalytic subunit
| 分子 | 名称: Serine/threonine-protein phosphatase PP1-alpha catalytic subunit タイプ: protein_or_peptide / ID: 2 / コピー数: 1 / 光学異性体: LEVO / EC番号: protein-serine/threonine phosphatase |
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| 由来(天然) | 生物種: Homo sapiens (ヒト) |
| 分子量 | 理論値: 37.514039 KDa |
| 組換発現 | 生物種: ![]() |
| 配列 | 文字列: MSDSEKLNLD SIIGRLLEVQ GSRPGKNVQL TENEIRGLCL KSREIFLSQP ILLELEAPLK ICGAIHGQYY DLLRLFEYGG FPPESNYLF LGDYVDRGKQ SLETICLLLA YKIKYPENFF LLRGNHECAS INRIYGFYDE CKRRYNIKLW KTFTDCFNCL P IAAIVDEK ...文字列: MSDSEKLNLD SIIGRLLEVQ GSRPGKNVQL TENEIRGLCL KSREIFLSQP ILLELEAPLK ICGAIHGQYY DLLRLFEYGG FPPESNYLF LGDYVDRGKQ SLETICLLLA YKIKYPENFF LLRGNHECAS INRIYGFYDE CKRRYNIKLW KTFTDCFNCL P IAAIVDEK IFCCHGGLSP DLQSMEQIRR IMRPTDVPDQ GLLCDLLWSD PDKDVQGWGE NDRGVSFTFG AEVVAKFLHK HD LDLICRA HQVVEDGYEF FAKRQLVTLF SAPNYCGEFD NAGAMMSVDE TLMCSFQILK PADKNKGKYG QFSGLNPGGR PIT PPRNSA KAKK UniProtKB: Serine/threonine-protein phosphatase PP1-alpha catalytic subunit |
-分子 #3: Actin, alpha skeletal muscle
| 分子 | 名称: Actin, alpha skeletal muscle / タイプ: protein_or_peptide / ID: 3 / コピー数: 1 / 光学異性体: LEVO |
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| 由来(天然) | 生物種: ![]() |
| 分子量 | 理論値: 42.096953 KDa |
| 配列 | 文字列: MCDEDETTAL VCDNGSGLVK AGFAGDDAPR AVFPSIVGRP RHQGVMVGMG QKDSYVGDEA QSKRGILTLK YPIEHGIITN WDDMEKIWH HTFYNELRVA PEEHPTLLTE APLNPKANRE KMTQIMFETF NVPAMYVAIQ AVLSLYASGR TTGIVLDSGD G VTHNVPIY ...文字列: MCDEDETTAL VCDNGSGLVK AGFAGDDAPR AVFPSIVGRP RHQGVMVGMG QKDSYVGDEA QSKRGILTLK YPIEHGIITN WDDMEKIWH HTFYNELRVA PEEHPTLLTE APLNPKANRE KMTQIMFETF NVPAMYVAIQ AVLSLYASGR TTGIVLDSGD G VTHNVPIY EGYALPHAIM RLDLAGRDLT DYLMKILTER GYSFVTTAER EIVRDIKEKL CYVALDFENE MATAASSSSL EK SYELPDG QVITIGNERF RCPETLFQPS FIGMESAGIH ETTYNSIMKC DIDIRKDLYA NNVMSGGTTM YPGIADRMQK EIT ALAPST MKIKIIAPPE RKYSVWIGGS ILASLSTFQQ MWITKQEYDE AGPSIVHRKC F UniProtKB: Actin, alpha skeletal muscle |
-分子 #4: Deoxyribonuclease-1
| 分子 | 名称: Deoxyribonuclease-1 / タイプ: protein_or_peptide / ID: 4 / コピー数: 1 / 光学異性体: LEVO / EC番号: deoxyribonuclease I |
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| 由来(天然) | 生物種: ![]() |
| 分子量 | 理論値: 31.374436 KDa |
| 配列 | 文字列: MRGTRLMGLL LALAGLLQLG LSLKIAAFNI RTFGETKMSN ATLASYIVRI VRRYDIVLIQ EVRDSHLVAV GKLLDYLNQD DPNTYHYVV SEPLGRNSYK ERYLFLFRPN KVSVLDTYQY DDGCESCGND SFSREPAVVK FSSHSTKVKE FAIVALHSAP S DAVAEINS ...文字列: MRGTRLMGLL LALAGLLQLG LSLKIAAFNI RTFGETKMSN ATLASYIVRI VRRYDIVLIQ EVRDSHLVAV GKLLDYLNQD DPNTYHYVV SEPLGRNSYK ERYLFLFRPN KVSVLDTYQY DDGCESCGND SFSREPAVVK FSSHSTKVKE FAIVALHSAP S DAVAEINS LYDVYLDVQQ KWHLNDVMLM GDFNADCSYV TSSQWSSIRL RTSSTFQWLI PDSADTTATS TNCAYDRIVV AG SLLQSSV VPGSAAPFDF QAAYGLSNEM ALAISDHYPV EVTLT UniProtKB: Deoxyribonuclease-1 |
-分子 #5: Eukaryotic translation initiation factor 2 subunit 1
| 分子 | 名称: Eukaryotic translation initiation factor 2 subunit 1 タイプ: protein_or_peptide / ID: 5 / コピー数: 1 / 光学異性体: LEVO |
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| 由来(天然) | 生物種: Homo sapiens (ヒト) |
| 分子量 | 理論値: 21.817863 KDa |
| 組換発現 | 生物種: ![]() |
| 配列 | 文字列: PGLSCRFYQH KFPEVEDVVM VNVRSIAEMG AYVSLLEYNN IEGMILLSEL (SEP)RRRIRSINK LIRIGRNECV VVIRVD KEK GYIDLSKRRV SPEEAIKCED KFTKSKTVYS ILRHVAEVLE YTKDEQLESL FQRTAWVFDD KYKRPGYGAY DAFKHAV SD ...文字列: PGLSCRFYQH KFPEVEDVVM VNVRSIAEMG AYVSLLEYNN IEGMILLSEL (SEP)RRRIRSINK LIRIGRNECV VVIRVD KEK GYIDLSKRRV SPEEAIKCED KFTKSKTVYS ILRHVAEVLE YTKDEQLESL FQRTAWVFDD KYKRPGYGAY DAFKHAV SD PSILDSLDLN EDEREVLINN INRRLTPQ UniProtKB: Eukaryotic translation initiation factor 2 subunit 1 |
-分子 #6: MANGANESE (II) ION
| 分子 | 名称: MANGANESE (II) ION / タイプ: ligand / ID: 6 / コピー数: 1 / 式: MN |
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| 分子量 | 理論値: 54.938 Da |
-分子 #7: CALCIUM ION
| 分子 | 名称: CALCIUM ION / タイプ: ligand / ID: 7 / コピー数: 1 / 式: CA |
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| 分子量 | 理論値: 40.078 Da |
-分子 #8: ADENOSINE-5'-TRIPHOSPHATE
| 分子 | 名称: ADENOSINE-5'-TRIPHOSPHATE / タイプ: ligand / ID: 8 / コピー数: 1 / 式: ATP |
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| 分子量 | 理論値: 507.181 Da |
| Chemical component information | ![]() ChemComp-ATP: |
-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 |
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試料調製
| 濃度 | 5.5 mg/mL | |||||||||||||||||||||
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| 緩衝液 | pH: 7.5 構成要素:
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| グリッド | モデル: Quantifoil R1.2/1.3 / 材質: GOLD / メッシュ: 300 / 支持フィルム - 材質: GOLD / 支持フィルム - トポロジー: HOLEY / 支持フィルム - Film thickness: 25 / 前処理 - タイプ: GLOW DISCHARGE / 前処理 - 時間: 45 sec. / 前処理 - 雰囲気: AIR / 前処理 - 気圧: 0.045 kPa | |||||||||||||||||||||
| 凍結 | 凍結剤: ETHANE / チャンバー内湿度: 100 % / チャンバー内温度: 278 K / 装置: FEI VITROBOT MARK IV / 詳細: 3.5 uL volume, -5 blot force, 1.5 blot time. |
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電子顕微鏡法
| 顕微鏡 | TFS KRIOS |
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| 特殊光学系 | エネルギーフィルター - 名称: TFS Selectris X / エネルギーフィルター - スリット幅: 10 eV |
| 撮影 | フィルム・検出器のモデル: TFS FALCON 4i (4k x 4k) 撮影したグリッド数: 1 / 実像数: 5236 / 平均電子線量: 50.0 e/Å2 |
| 電子線 | 加速電圧: 300 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 / Cs: 2.7 mm / 最大 デフォーカス(公称値): 1.8 µm / 最小 デフォーカス(公称値): 0.8 µm / 倍率(公称値): 130000 |
| 試料ステージ | 試料ホルダーモデル: FEI TITAN KRIOS AUTOGRID HOLDER ホルダー冷却材: NITROGEN |
| 実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |
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画像解析
-原子モデル構築 1
| 初期モデル | Chain - Source name: AlphaFold / Chain - Initial model type: in silico model |
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| 得られたモデル | ![]() PDB-9nb9: |
ムービー
コントローラー
万見について




キーワード
Homo sapiens (ヒト)
African swine fever virus (アフリカ豚コレラウイルス)
データ登録者
引用





















Z (Sec.)
Y (Row.)
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FIELD EMISSION GUN
