+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-15606 | |||||||||
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タイトル | CryoEM structure of the human Nucleophosmin 1 core | |||||||||
マップデータ | ||||||||||
試料 |
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機能・相同性 | 機能・相同性情報 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 / unfolded protein binding / Signaling by ALK fusions and activated point mutants / 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 | Homo sapiens (ヒト) | |||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3.53 Å | |||||||||
データ登録者 | Valentin Gese G / Hallberg BM | |||||||||
資金援助 | スウェーデン, 1件
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引用 | ジャーナル: PNAS Nexus / 年: 2023 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. | |||||||||
履歴 |
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-構造の表示
添付画像 |
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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_15606.map.gz | 11.4 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-15606-v30.xml emd-15606.xml | 20.8 KB 20.8 KB | 表示 表示 | EMDBヘッダ |
FSC (解像度算出) | emd_15606_fsc.xml | 11.2 KB | 表示 | FSCデータファイル |
画像 | emd_15606.png | 81.1 KB | ||
マスクデータ | emd_15606_msk_1.map | 216 MB | マスクマップ | |
その他 | emd_15606_additional_1.map.gz emd_15606_additional_2.map.gz emd_15606_additional_3.map.gz emd_15606_half_map_1.map.gz emd_15606_half_map_2.map.gz | 171.1 MB 25.5 MB 25.4 MB 171.1 MB 171.1 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-15606 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-15606 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_15606_validation.pdf.gz | 756 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_15606_full_validation.pdf.gz | 755.6 KB | 表示 | |
XML形式データ | emd_15606_validation.xml.gz | 21.1 KB | 表示 | |
CIF形式データ | emd_15606_validation.cif.gz | 27.8 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-15606 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-15606 | HTTPS FTP |
-関連構造データ
関連構造データ | 8as5MC M: このマップから作成された原子モデル C: 同じ文献を引用 (文献) |
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類似構造データ | 類似検索 - 機能・相同性F&H 検索 |
-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 |
-マップ
ファイル | ダウンロード / ファイル: emd_15606.map.gz / 形式: CCP4 / 大きさ: 216 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: 0.505 Å | ||||||||||||||||||||||||||||||||||||
密度 |
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対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||
詳細 | EMDB XML:
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-添付データ
-マスク #1
ファイル | emd_15606_msk_1.map | ||||||||||||
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密度ヒストグラム |
-追加マップ: #1
ファイル | emd_15606_additional_1.map | ||||||||||||
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密度ヒストグラム |
-追加マップ: Nucleophosmin 1 class with weaker C-terminal domain density
ファイル | emd_15606_additional_2.map | ||||||||||||
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注釈 | Nucleophosmin 1 class with weaker C-terminal domain density | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-追加マップ: Nucleophosmin 1 class with stronger C-terminal domain density
ファイル | emd_15606_additional_3.map | ||||||||||||
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注釈 | Nucleophosmin 1 class with stronger C-terminal domain density | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: #2
ファイル | emd_15606_half_map_1.map | ||||||||||||
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投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: #1
ファイル | emd_15606_half_map_2.map | ||||||||||||
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投影像・断面図 |
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密度ヒストグラム |
-試料の構成要素
-全体 : Nucleophosmin 1
全体 | 名称: Nucleophosmin 1 |
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要素 |
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-超分子 #1: Nucleophosmin 1
超分子 | 名称: Nucleophosmin 1 / タイプ: complex / ID: 1 / キメラ: Yes / 親要素: 0 / 含まれる分子: all |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
-分子 #1: Nucleophosmin
分子 | 名称: Nucleophosmin / タイプ: protein_or_peptide / ID: 1 / コピー数: 5 / 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: 32.708141 KDa |
組換発現 | 生物種: Escherichia coli (大腸菌) |
配列 | 文字列: SMEDSMDMDM SPLRPQNYLF GCELKADKDY HFKVDNDENE HQLSLRTVSL GAGAKDELHI VEAEAMNYEG SPIKVTLATL KMSVQPTVS LGGFEITPPV VLRLKCGSGP VHISGQHLVA VEEDAESEDE EEEDVKLLSI SGKRSAPGGG SKVPQKKVKL A ADEDDDDD ...文字列: SMEDSMDMDM SPLRPQNYLF GCELKADKDY HFKVDNDENE HQLSLRTVSL GAGAKDELHI VEAEAMNYEG SPIKVTLATL KMSVQPTVS LGGFEITPPV VLRLKCGSGP VHISGQHLVA VEEDAESEDE EEEDVKLLSI SGKRSAPGGG SKVPQKKVKL A ADEDDDDD DEEDDDEDDD DDDFDDEEAE EKAPVKKSIR DTPAKNAQKS NQNGKDSKPS STPRSKGQES FKKQEKTPKT PK GPSSVED IKAKMQASIE KGGSLPKVEA KFINYVKNCF RMTDQEAIQD LWQWRKSL |
-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 |
-試料調製
濃度 | 0.75 mg/mL |
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緩衝液 | pH: 8 |
凍結 | 凍結剤: ETHANE / 装置: FEI VITROBOT MARK IV |
-電子顕微鏡法
顕微鏡 | TFS KRIOS |
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撮影 | フィルム・検出器のモデル: GATAN K3 BIOQUANTUM (6k x 4k) 平均電子線量: 54.0 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: SPOT SCAN / 撮影モード: BRIGHT FIELD / 最大 デフォーカス(公称値): 2.0 µm / 最小 デフォーカス(公称値): 0.5 µm |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |