+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-3914 | |||||||||||||||
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タイトル | Substrate processing state 26S proteasome (SPS1) | |||||||||||||||
マップデータ | in situ reconstruction of Rat proteasome in substrate processing states 1 | |||||||||||||||
試料 |
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キーワード | UPS / Substrate processing state / Neuron degeneration / HYDROLASE | |||||||||||||||
機能・相同性 | 機能・相同性情報 nuclear proteasome complex / Cross-presentation of soluble exogenous antigens (endosomes) / N-glycan trimming in the ER and Calnexin/Calreticulin cycle / Regulation of ornithine decarboxylase (ODC) / Metalloprotease DUBs / Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha / Autodegradation of Cdh1 by Cdh1:APC/C / SCF-beta-TrCP mediated degradation of Emi1 / APC/C:Cdc20 mediated degradation of Securin / APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1 ...nuclear proteasome complex / Cross-presentation of soluble exogenous antigens (endosomes) / N-glycan trimming in the ER and Calnexin/Calreticulin cycle / Regulation of ornithine decarboxylase (ODC) / Metalloprotease DUBs / Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha / Autodegradation of Cdh1 by Cdh1:APC/C / SCF-beta-TrCP mediated degradation of Emi1 / APC/C:Cdc20 mediated degradation of Securin / APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1 / Cdc20:Phospho-APC/C mediated degradation of Cyclin A / SCF(Skp2)-mediated degradation of p27/p21 / Autodegradation of the E3 ubiquitin ligase COP1 / Asymmetric localization of PCP proteins / Degradation of DVL / Hedgehog ligand biogenesis / Dectin-1 mediated noncanonical NF-kB signaling / Degradation of GLI1 by the proteasome / Hedgehog 'on' state / TNFR2 non-canonical NF-kB pathway / NIK-->noncanonical NF-kB signaling / UCH proteinases / Assembly of the pre-replicative complex / CDK-mediated phosphorylation and removal of Cdc6 / G2/M Checkpoints / Ubiquitin Mediated Degradation of Phosphorylated Cdc25A / Ubiquitin-dependent degradation of Cyclin D / The role of GTSE1 in G2/M progression after G2 checkpoint / FBXL7 down-regulates AURKA during mitotic entry and in early mitosis / RUNX1 regulates transcription of genes involved in differentiation of HSCs / Regulation of RUNX3 expression and activity / GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2 / GLI3 is processed to GLI3R by the proteasome / Activation of NF-kappaB in B cells / Degradation of beta-catenin by the destruction complex / Degradation of AXIN / Regulation of RAS by GAPs / Orc1 removal from chromatin / Neddylation / AUF1 (hnRNP D0) binds and destabilizes mRNA / MAPK6/MAPK4 signaling / Regulation of PTEN stability and activity / KEAP1-NFE2L2 pathway / Separation of Sister Chromatids / fluid transport / Antigen processing: Ubiquitination & Proteasome degradation / regulation of protein catabolic process at postsynapse, modulating synaptic transmission / ABC-family proteins mediated transport / Ub-specific processing proteases / positive regulation of inclusion body assembly / thyrotropin-releasing hormone receptor binding / modulation by host of viral transcription / meiosis I / proteasome accessory complex / integrator complex / proteasome regulatory particle / cytosolic proteasome complex / proteasome regulatory particle, lid subcomplex / proteasome-activating activity / proteasome regulatory particle, base subcomplex / metal-dependent deubiquitinase activity / proteasome core complex / Neutrophil degranulation / myofibril / immune system process / proteasome binding / regulation of protein catabolic process / proteasome storage granule / blastocyst development / general transcription initiation factor binding / NF-kappaB binding / endopeptidase activator activity / polyubiquitin modification-dependent protein binding / proteasome assembly / protein deubiquitination / positive regulation of RNA polymerase II transcription preinitiation complex assembly / proteasome endopeptidase complex / proteasome core complex, beta-subunit complex / proteasome core complex, alpha-subunit complex / threonine-type endopeptidase activity / mRNA export from nucleus / regulation of proteasomal protein catabolic process / enzyme regulator activity / inclusion body / ERAD pathway / TBP-class protein binding / sarcomere / proteasome complex / ciliary basal body / proteolysis involved in protein catabolic process / stem cell differentiation / negative regulation of inflammatory response to antigenic stimulus / lipopolysaccharide binding / double-strand break repair via homologous recombination / P-body / modulation of chemical synaptic transmission / response to virus / response to organic cyclic compound / double-strand break repair via nonhomologous end joining / nuclear matrix 類似検索 - 分子機能 | |||||||||||||||
生物種 | Rattus norvegicus (ドブネズミ) | |||||||||||||||
手法 | サブトモグラム平均法 / クライオ電子顕微鏡法 / 解像度: 15.4 Å | |||||||||||||||
データ登録者 | Guo Q / Lehmer C | |||||||||||||||
資金援助 | ドイツ, 米国, 4件
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引用 | ジャーナル: Cell / 年: 2018 タイトル: In Situ Structure of Neuronal C9orf72 Poly-GA Aggregates Reveals Proteasome Recruitment. 著者: Qiang Guo / Carina Lehmer / Antonio Martínez-Sánchez / Till Rudack / Florian Beck / Hannelore Hartmann / Manuela Pérez-Berlanga / Frédéric Frottin / Mark S Hipp / F Ulrich Hartl / Dieter ...著者: Qiang Guo / Carina Lehmer / Antonio Martínez-Sánchez / Till Rudack / Florian Beck / Hannelore Hartmann / Manuela Pérez-Berlanga / Frédéric Frottin / Mark S Hipp / F Ulrich Hartl / Dieter Edbauer / Wolfgang Baumeister / Rubén Fernández-Busnadiego / 要旨: Protein aggregation and dysfunction of the ubiquitin-proteasome system are hallmarks of many neurodegenerative diseases. Here, we address the elusive link between these phenomena by employing cryo- ...Protein aggregation and dysfunction of the ubiquitin-proteasome system are hallmarks of many neurodegenerative diseases. Here, we address the elusive link between these phenomena by employing cryo-electron tomography to dissect the molecular architecture of protein aggregates within intact neurons at high resolution. We focus on the poly-Gly-Ala (poly-GA) aggregates resulting from aberrant translation of an expanded GGGGCC repeat in C9orf72, the most common genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia. We find that poly-GA aggregates consist of densely packed twisted ribbons that recruit numerous 26S proteasome complexes, while other macromolecules are largely excluded. Proximity to poly-GA ribbons stabilizes a transient substrate-processing conformation of the 26S proteasome, suggesting stalled degradation. Thus, poly-GA aggregates may compromise neuronal proteostasis by driving the accumulation and functional impairment of a large fraction of cellular proteasomes. | |||||||||||||||
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 | EMマップ: SurfViewMolmilJmol/JSmol |
添付画像 |
-ダウンロードとリンク
-EMDBアーカイブ
マップデータ | emd_3914.map.gz | 2.6 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-3914-v30.xml emd-3914.xml | 52 KB 52 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_3914.png | 58.5 KB | ||
Filedesc metadata | emd-3914.cif.gz | 14.1 KB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-3914 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-3914 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_3914_validation.pdf.gz | 236.9 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_3914_full_validation.pdf.gz | 236 KB | 表示 | |
XML形式データ | emd_3914_validation.xml.gz | 5.2 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-3914 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-3914 | HTTPS FTP |
-関連構造データ
-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_3914.map.gz / 形式: CCP4 / 大きさ: 2.8 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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注釈 | in situ reconstruction of Rat proteasome in substrate processing states 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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: 3.42 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
密度 |
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対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
詳細 | EMDB XML:
CCP4マップ ヘッダ情報:
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-添付データ
-試料の構成要素
+全体 : Substrate processing state 26S proteasome (SPS1)
+超分子 #1: Substrate processing state 26S proteasome (SPS1)
+分子 #1: Proteasome subunit alpha type-6
+分子 #2: Proteasome subunit alpha type-2
+分子 #3: Proteasome subunit alpha type-4
+分子 #4: Proteasome subunit alpha type-7
+分子 #5: Proteasome subunit alpha type-5
+分子 #6: Proteasome subunit alpha type-1
+分子 #7: Proteasome subunit alpha type-3
+分子 #8: Proteasome subunit beta type-6
+分子 #9: Proteasome subunit beta type-7
+分子 #10: Proteasome subunit beta type-3
+分子 #11: Proteasome subunit beta type-2
+分子 #12: Proteasome subunit beta type-5
+分子 #13: Proteasome subunit beta type-1
+分子 #14: Proteasome subunit beta type-4
+分子 #15: 26S proteasome subunit S5a
+分子 #16: Proteasome (Prosome, macropain) 26S subunit, non-ATPase, 14
+分子 #17: Proteasome 26S subunit, non-ATPase 8
+分子 #18: RCG28037
+分子 #19: 26S proteasome non-ATPase regulatory subunit 2
+分子 #20: 26S proteasome non-ATPase regulatory subunit 1
+分子 #21: Proteasome (Prosome, macropain) 26S subunit, non-ATPase, 3
+分子 #22: Proteasome (Prosome, macropain) 26S subunit, non-ATPase, 12
+分子 #23: 26S proteasome non-ATPase regulatory subunit 11
+分子 #24: Proteasome (Prosome, macropain) 26S subunit, non-ATPase, 6
+分子 #25: Proteasome (Prosome, macropain) 26S subunit, non-ATPase, 7 (Predicted)
+分子 #26: 26S proteasome non-ATPase regulatory subunit 13
+分子 #27: 26S proteasome regulatory subunit 7
+分子 #28: 26S proteasome regulatory subunit 4
+分子 #29: 26S proteasome regulatory subunit 6B
+分子 #30: Proteasome 26S subunit, ATPase 6
+分子 #31: 26S proteasome regulatory subunit 6A
+分子 #32: 26S proteasome regulatory subunit 8
-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 | サブトモグラム平均法 |
試料の集合状態 | cell |
-試料調製
緩衝液 | pH: 7 |
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グリッド | モデル: Quantifoil R2/1 / 材質: GOLD / メッシュ: 200 / 支持フィルム - 材質: CARBON / 支持フィルム - トポロジー: HOLEY / 前処理 - タイプ: GLOW DISCHARGE / 前処理 - 時間: 30 sec. / 前処理 - 雰囲気: AIR / 詳細: The grid was coated with C prior to use |
凍結 | 凍結剤: ETHANE-PROPANE / チャンバー内湿度: 100 % / チャンバー内温度: 298 K / 装置: FEI VITROBOT MARK IV |
詳細 | FIB milled rat primary neurons |
-電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
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撮影 | フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) 検出モード: COUNTING / デジタル化 - サイズ - 横: 3838 pixel / デジタル化 - サイズ - 縦: 3710 pixel / 平均露光時間: 2.0 sec. / 平均電子線量: 1.8 e/Å2 |
電子線 | 加速電圧: 300 kV / 電子線源: FIELD EMISSION GUN |
電子光学系 | C2レンズ絞り径: 70.0 µm / 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): 7.0 µm / 最小 デフォーカス(公称値): 5.0 µm / 倍率(公称値): 42000 |
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 |
-画像解析
最終 再構成 | 想定した対称性 - 点群: C1 (非対称) / 解像度のタイプ: BY AUTHOR / 解像度: 15.4 Å / 解像度の算出法: FSC 0.143 CUT-OFF / ソフトウェア - 名称: RELION (ver. 1.4) / 使用したサブトモグラム数: 2136 |
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抽出 | トモグラム数: 9 / 使用した粒子像数: 10367 / 参照モデル: average of manual picked subtomograms / 手法: Template matching ソフトウェア: (名称: PyTom, TOM Toolbox, RELION (ver. 1.4)) |
最終 3次元分類 | クラス数: 4 / ソフトウェア - 名称: RELION (ver. 1.4) |
最終 角度割当 | タイプ: PROJECTION MATCHING / ソフトウェア - 名称: RELION (ver. 1.4) |
-原子モデル構築 1
精密化 | プロトコル: FLEXIBLE FIT |
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得られたモデル | PDB-6epd: |