+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-8333 | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
タイトル | Structural basis for dynamic regulation of the human 26S proteasome | |||||||||
マップデータ | The doubly capped human 26S proteasome reconstruction from 237083 particles. The refinement was focused on the core particle. | |||||||||
試料 |
| |||||||||
機能・相同性 | 機能・相同性情報 positive regulation of inclusion body assembly / Impaired BRCA2 translocation to the nucleus / Impaired BRCA2 binding to SEM1 (DSS1) / thyrotropin-releasing hormone receptor binding / modulation by host of viral transcription / 加水分解酵素; プロテアーゼ; ペプチド結合加水分解酵素; オメガペプチターゼ / proteasome accessory complex / integrator complex / purine ribonucleoside triphosphate binding / meiosis I ...positive regulation of inclusion body assembly / Impaired BRCA2 translocation to the nucleus / Impaired BRCA2 binding to SEM1 (DSS1) / thyrotropin-releasing hormone receptor binding / modulation by host of viral transcription / 加水分解酵素; プロテアーゼ; ペプチド結合加水分解酵素; オメガペプチターゼ / proteasome accessory complex / integrator complex / purine ribonucleoside triphosphate binding / meiosis I / positive regulation of proteasomal protein catabolic process / proteasome regulatory particle / cytosolic proteasome complex / proteasome regulatory particle, lid subcomplex / proteasome-activating activity / metal-dependent deubiquitinase activity / protein K63-linked deubiquitination / proteasome regulatory particle, base subcomplex / regulation of endopeptidase activity / negative regulation of programmed cell death / Defective homologous recombination repair (HRR) due to BRCA1 loss of function / Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function / Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function / Homologous DNA Pairing and Strand Exchange / Regulation of ornithine decarboxylase (ODC) / Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA) / proteasome core complex / Resolution of D-loop Structures through Holliday Junction Intermediates / Cross-presentation of soluble exogenous antigens (endosomes) / Somitogenesis / K63-linked deubiquitinase activity / Impaired BRCA2 binding to RAD51 / immune system process / myofibril / proteasome binding / regulation of protein catabolic process / proteasome storage granule / Presynaptic phase of homologous DNA pairing and strand exchange / transcription factor binding / blastocyst development / general transcription initiation factor binding / endopeptidase activator activity / NF-kappaB binding / proteasome assembly / polyubiquitin modification-dependent protein binding / proteasome endopeptidase complex / positive regulation of RNA polymerase II transcription preinitiation complex assembly / proteasome core complex, beta-subunit complex / proteasome core complex, alpha-subunit complex / threonine-type endopeptidase activity / mRNA export from nucleus / enzyme regulator activity / regulation of proteasomal protein catabolic process / SARS-CoV-1 targets host intracellular signalling and regulatory pathways / ERAD pathway / inclusion body / negative regulation of inflammatory response to antigenic stimulus / : / sarcomere / proteasome complex / Regulation of activated PAK-2p34 by proteasome mediated degradation / ciliary basal body / N-glycan trimming in the ER and Calnexin/Calreticulin cycle / proteolysis involved in protein catabolic process / Autodegradation of Cdh1 by Cdh1:APC/C / APC/C:Cdc20 mediated degradation of Securin / Asymmetric localization of PCP proteins / SCF-beta-TrCP mediated degradation of Emi1 / NIK-->noncanonical NF-kB signaling / Ubiquitin-dependent degradation of Cyclin D / AUF1 (hnRNP D0) binds and destabilizes mRNA / TNFR2 non-canonical NF-kB pathway / Assembly of the pre-replicative complex / Vpu mediated degradation of CD4 / Degradation of DVL / stem cell differentiation / Ubiquitin Mediated Degradation of Phosphorylated Cdc25A / Dectin-1 mediated noncanonical NF-kB signaling / Cdc20:Phospho-APC/C mediated degradation of Cyclin A / Hh mutants are degraded by ERAD / lipopolysaccharide binding / Degradation of AXIN / Degradation of GLI1 by the proteasome / Activation of NF-kappaB in B cells / Hedgehog ligand biogenesis / Defective CFTR causes cystic fibrosis / Negative regulation of NOTCH4 signaling / GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2 / G2/M Checkpoints / Vif-mediated degradation of APOBEC3G / Autodegradation of the E3 ubiquitin ligase COP1 / Hedgehog 'on' state / Regulation of RUNX3 expression and activity / Degradation of GLI2 by the proteasome / GLI3 is processed to GLI3R by the proteasome / P-body / FBXL7 down-regulates AURKA during mitotic entry and in early mitosis / MAPK6/MAPK4 signaling / double-strand break repair via homologous recombination / APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1 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: 3.8 Å | |||||||||
データ登録者 | Chen S / Wu J / Lu Y / Ma YB / Lee BH / Yu Z / Ouyang Q / Finley D / Kirschner MW / Mao Y | |||||||||
引用 | ジャーナル: Proc Natl Acad Sci U S A / 年: 2016 タイトル: Structural basis for dynamic regulation of the human 26S proteasome. 著者: Shuobing Chen / Jiayi Wu / Ying Lu / Yong-Bei Ma / Byung-Hoon Lee / Zhou Yu / Qi Ouyang / Daniel J Finley / Marc W Kirschner / Youdong Mao / 要旨: The proteasome is the major engine of protein degradation in all eukaryotic cells. At the heart of this machine is a heterohexameric ring of AAA (ATPases associated with diverse cellular activities) ...The proteasome is the major engine of protein degradation in all eukaryotic cells. At the heart of this machine is a heterohexameric ring of AAA (ATPases associated with diverse cellular activities) proteins that unfolds ubiquitylated target proteins that are concurrently translocated into a proteolytic chamber and degraded into peptides. Using cryoelectron microscopy, we determined a near-atomic-resolution structure of the 2.5-MDa human proteasome in its ground state, as well as subnanometer-resolution structures of the holoenzyme in three alternative conformational states. The substrate-unfolding AAA-ATPase channel is narrowed by 10 inward-facing pore loops arranged into two helices that run in parallel with each other, one hydrophobic in character and the other highly charged. The gate of the core particle was unexpectedly found closed in the ground state and open in only one of the alternative states. Coordinated, stepwise conformational changes of the regulatory particle couple ATP hydrolysis to substrate translocation and regulate gating of the core particle, leading to processive degradation. | |||||||||
履歴 |
|
-構造の表示
ムービー |
ムービービューア |
---|---|
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_8333.map.gz | 917.8 MB | EMDBマップデータ形式 | |
---|---|---|---|---|
ヘッダ (付随情報) | emd-8333-v30.xml emd-8333.xml | 14.7 KB 14.7 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_8333.png | 44 KB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-8333 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-8333 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_8333_validation.pdf.gz | 403.1 KB | 表示 | EMDB検証レポート |
---|---|---|---|---|
文書・詳細版 | emd_8333_full_validation.pdf.gz | 402.7 KB | 表示 | |
XML形式データ | emd_8333_validation.xml.gz | 8.5 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-8333 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-8333 | HTTPS FTP |
-関連構造データ
関連構造データ | 5t0cMC 8332C 8334C 8335C 8336C 8337C 5t0gC 5t0hC 5t0iC 5t0jC C: 同じ文献を引用 (文献) M: このマップから作成された原子モデル |
---|---|
類似構造データ | |
電子顕微鏡画像生データ | EMPIAR-10072 (タイトル: Structural basis for dynamic regulation of the human 26S proteasome Data size: 2.0 TB Data #1: Drift-corrected micrographs of human 26S proteasome holoenzyme [micrographs - single frame] Data #2: Classified particle datasets for the human proteasome in four conformational states [picked particles - multiframe - processed]) |
-リンク
EMDBのページ | EMDB (EBI/PDBe) / EMDataResource |
---|---|
「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_8333.map.gz / 形式: CCP4 / 大きさ: 1000 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
注釈 | The doubly capped human 26S proteasome reconstruction from 237083 particles. The refinement was focused on the core particle. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 0.86 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
密度 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
詳細 | EMDB XML:
CCP4マップ ヘッダ情報:
|
-添付データ
-試料の構成要素
-全体 : 26S proteasome holoenzyme
全体 | 名称: 26S proteasome holoenzyme |
---|---|
要素 |
|
-超分子 #1: 26S proteasome holoenzyme
超分子 | 名称: 26S proteasome holoenzyme / タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1 |
---|---|
由来(天然) | 生物種: Homo sapiens (ヒト) |
分子量 | 実験値: 2.5 MDa |
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
---|---|
解析 | 単粒子再構成法 |
試料の集合状態 | particle |
-試料調製
濃度 | 1.5 mg/mL | ||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
緩衝液 | pH: 7.5 構成要素:
| ||||||||||||||||||
グリッド | モデル: C-Flat R1/1 / 材質: COPPER / メッシュ: 400 / 支持フィルム - 材質: CARBON / 支持フィルム - トポロジー: HOLEY ARRAY / 支持フィルム - Film thickness: 50.0 nm / 前処理 - タイプ: GLOW DISCHARGE / 前処理 - 雰囲気: AIR | ||||||||||||||||||
凍結 | 凍結剤: ETHANE / チャンバー内湿度: 100 % / チャンバー内温度: 277 K / 装置: FEI VITROBOT MARK IV / 詳細: blotted for 2 seconds, blotting force 3. |
-電子顕微鏡法
顕微鏡 | FEI TECNAI ARCTICA |
---|---|
撮影 | フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) 検出モード: SUPER-RESOLUTION / デジタル化 - サイズ - 横: 7420 pixel / デジタル化 - サイズ - 縦: 7676 pixel / デジタル化 - サンプリング間隔: 5.0 µm / デジタル化 - 画像ごとのフレーム数: 3-20 / 撮影したグリッド数: 12 / 実像数: 10367 / 平均露光時間: 9.0 sec. / 平均電子線量: 30.0 e/Å2 |
電子線 | 加速電圧: 200 kV / 電子線源: FIELD EMISSION GUN |
電子光学系 | C2レンズ絞り径: 50.0 µm / 倍率(補正後): 28736 / 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): -3.0 µm / 最小 デフォーカス(公称値): -1.0 µm / 倍率(公称値): 21000 |
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: Talos Arctica / 画像提供: FEI Company |
+画像解析
-原子モデル構築 1
精密化 | 空間: RECIPROCAL / プロトコル: AB INITIO MODEL / 温度因子: 80 |
---|---|
得られたモデル | PDB-5t0c: |