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データを開く
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基本情報
登録情報 | データベース: PDB / ID: 8as5 | ||||||
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タイトル | CryoEM structure of the human Nucleophosmin 1 core | ||||||
![]() | Nucleophosmin | ||||||
![]() | CHAPERONE / Phase separation | ||||||
機能・相同性 | ![]() regulation of eIF2 alpha phosphorylation by dsRNA / regulation of mRNA stability involved in cellular response to UV / regulation of endoribonuclease activity / negative regulation of centrosome duplication / regulation of endodeoxyribonuclease activity / positive regulation of cell cycle G2/M phase transition / regulation of centriole replication / granular component / TFAP2A acts as a transcriptional repressor during retinoic acid induced cell differentiation / negative regulation of protein kinase activity by regulation of protein phosphorylation ...regulation of eIF2 alpha phosphorylation by dsRNA / regulation of mRNA stability involved in cellular response to UV / regulation of endoribonuclease activity / negative regulation of centrosome duplication / regulation of endodeoxyribonuclease activity / positive regulation of cell cycle G2/M phase transition / regulation of centriole replication / granular component / TFAP2A acts as a transcriptional repressor during retinoic acid induced cell differentiation / negative regulation of protein kinase activity by regulation of protein phosphorylation / SARS-CoV-1-host interactions / Tat protein binding / regulation of centrosome duplication / ALK mutants bind TKIs / spindle pole centrosome / Nuclear import of Rev protein / centrosome cycle / nucleocytoplasmic transport / TP53 regulates transcription of additional cell cycle genes whose exact role in the p53 pathway remain uncertain / protein kinase inhibitor activity / ribosomal large subunit binding / ribosomal small subunit binding / NF-kappaB binding / ribosomal large subunit export from nucleus / ribosomal small subunit export from nucleus / Nuclear events stimulated by ALK signaling in cancer / ribosomal subunit export from nucleus / core promoter sequence-specific DNA binding / Deposition of new CENPA-containing nucleosomes at the centromere / ribosome assembly / SUMOylation of transcription cofactors / ribosomal large subunit biogenesis / positive regulation of translation / protein-DNA complex / intracellular protein transport / PKR-mediated signaling / protein localization / : / cellular response to UV / cellular senescence / Signaling by ALK fusions and activated point mutants / unfolded protein binding / nucleosome assembly / ribosomal small subunit biogenesis / positive regulation of NF-kappaB transcription factor activity / histone binding / DNA-binding transcription factor binding / transcription coactivator activity / rRNA binding / chromatin remodeling / ribonucleoprotein complex / negative regulation of cell population proliferation / DNA repair / focal adhesion / centrosome / chromatin binding / positive regulation of cell population proliferation / nucleolus / negative regulation of apoptotic process / protein kinase binding / positive regulation of DNA-templated transcription / signal transduction / protein homodimerization activity / positive regulation of transcription by RNA polymerase II / protein-containing complex / RNA binding / nucleoplasm / membrane / nucleus / 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: 3.53 Å | ||||||
![]() | Valentin Gese, G. / Hallberg, B.M. | ||||||
資金援助 | ![]()
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![]() | ![]() タイトル: A "grappling hook" interaction connects self-assembly and chaperone activity of Nucleophosmin 1. 著者: Mihkel Saluri / Axel Leppert / Genis Valentin Gese / Cagla Sahin / Dilraj Lama / Margit Kaldmäe / Gefei Chen / Arne Elofsson / Timothy M Allison / Marie Arsenian-Henriksson / Jan Johansson / ...著者: Mihkel Saluri / Axel Leppert / Genis Valentin Gese / Cagla Sahin / Dilraj Lama / Margit Kaldmäe / Gefei Chen / Arne Elofsson / Timothy M Allison / Marie Arsenian-Henriksson / Jan Johansson / David P Lane / B Martin Hällberg / Michael Landreh / ![]() ![]() ![]() 要旨: How the self-assembly of partially disordered proteins generates functional compartments in the cytoplasm and particularly in the nucleus is poorly understood. Nucleophosmin 1 (NPM1) is an abundant ...How the self-assembly of partially disordered proteins generates functional compartments in the cytoplasm and particularly in the nucleus is poorly understood. Nucleophosmin 1 (NPM1) is an abundant nucleolar protein that forms large oligomers and undergoes liquid-liquid phase separation by binding RNA or ribosomal proteins. It provides the scaffold for ribosome assembly but also prevents protein aggregation as part of the cellular stress response. Here, we use aggregation assays and native mass spectrometry (MS) to examine the relationship between the self-assembly and chaperone activity of NPM1. We find that oligomerization of full-length NPM1 modulates its ability to retard amyloid formation in vitro. Machine learning-based structure prediction and cryo-electron microscopy reveal fuzzy interactions between the acidic disordered region and the C-terminal nucleotide-binding domain, which cross-link NPM1 pentamers into partially disordered oligomers. The addition of basic peptides results in a tighter association within the oligomers, reducing their capacity to prevent amyloid formation. Together, our findings show that NPM1 uses a "grappling hook" mechanism to form a network-like structure that traps aggregation-prone proteins. Nucleolar proteins and RNAs simultaneously modulate the association strength and chaperone activity, suggesting a mechanism by which nucleolar composition regulates the chaperone activity of NPM1. | ||||||
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構造の表示
構造ビューア | 分子: ![]() ![]() |
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PDBx/mmCIF形式 | ![]() | 113.9 KB | 表示 | ![]() |
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-検証レポート
文書・要旨 | ![]() | 1.1 MB | 表示 | ![]() |
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文書・詳細版 | ![]() | 1.1 MB | 表示 | |
XML形式データ | ![]() | 35.1 KB | 表示 | |
CIF形式データ | ![]() | 49.9 KB | 表示 | |
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-関連構造データ
関連構造データ | ![]() 15606MC M: このデータのモデリングに利用したマップデータ C: 同じ文献を引用 ( |
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類似構造データ | 類似検索 - 機能・相同性 ![]() |
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リンク
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集合体
登録構造単位 | ![]()
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非結晶学的対称性 (NCS) | NCSドメイン:
NCSドメイン領域:
NCSアンサンブル:
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要素
#1: タンパク質 | 分子量: 32708.141 Da / 分子数: 5 / 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 | 名称: Nucleophosmin 1 / タイプ: COMPLEX / Entity ID: all / 由来: RECOMBINANT |
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分子量 | 実験値: NO |
由来(天然) | 生物種: ![]() |
由来(組換発現) | 生物種: ![]() ![]() |
緩衝液 | pH: 8 |
試料 | 濃度: 0.75 mg/ml / 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES |
急速凍結 | 装置: FEI VITROBOT MARK IV / 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: TFS KRIOS |
電子銃 | 電子線源: ![]() |
電子レンズ | モード: BRIGHT FIELD / 最大 デフォーカス(公称値): 2000 nm / 最小 デフォーカス(公称値): 500 nm |
撮影 | 電子線照射量: 54 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: REFMAC / バージョン: 5.8.0352 / 分類: 精密化 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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EMソフトウェア |
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CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
3次元再構成 | 解像度: 3.53 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 106905 / 対称性のタイプ: POINT | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
原子モデル構築 | プロトコル: FLEXIBLE FIT / 空間: RECIPROCAL | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
原子モデル構築 | PDB-ID: 5EHD | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
精密化 | 解像度: 2.5→91.91 Å / Cor.coef. Fo:Fc: 0.918 / WRfactor Rwork: 0.53 / SU B: 26.486 / SU ML: 0.458 / Average fsc free: 0 / Average fsc overall: 0.3441 / Average fsc work: 0.3441 / 交差検証法: NONE / ESU R: 0.294 / 詳細: Hydrogens have been added in their riding positions
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溶媒の処理 | 溶媒モデル: NONE | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
原子変位パラメータ | Biso mean: 126.735 Å2 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
精密化ステップ | サイクル: 1 / 合計: 3673 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
拘束条件 |
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