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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 | Focused refinement of 19S in the substrate-engaged human 26S proteasome bound to midnolin with RPT6 at top of spiral staircase | |||||||||
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試料 |
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キーワード | Midnolin / 26S proteasome / Complex / HYDROLASE | |||||||||
| 機能・相同性 | 機能・相同性情報thyrotropin-releasing hormone receptor binding / Impaired BRCA2 translocation to the nucleus / Impaired BRCA2 binding to SEM1 (DSS1) / nuclear proteasome complex / host-mediated perturbation of viral transcription / positive regulation of inclusion body assembly / integrator complex / proteasome accessory complex / meiosis I / proteasome regulatory particle ...thyrotropin-releasing hormone receptor binding / Impaired BRCA2 translocation to the nucleus / Impaired BRCA2 binding to SEM1 (DSS1) / nuclear proteasome complex / host-mediated perturbation of viral transcription / positive regulation of inclusion body assembly / integrator complex / proteasome accessory complex / meiosis I / proteasome regulatory particle / cytosolic proteasome complex / positive regulation of proteasomal protein catabolic process / proteasome-activating activity / proteasome regulatory particle, lid subcomplex / proteasome regulatory particle, base subcomplex / protein K63-linked deubiquitination / negative regulation of programmed cell death / metal-dependent deubiquitinase activity / Regulation of ornithine decarboxylase (ODC) / Proteasome assembly / Cross-presentation of soluble exogenous antigens (endosomes) / Somitogenesis / K63-linked deubiquitinase activity / transcription factor binding / Homologous DNA Pairing and Strand Exchange / 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 / Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA) / Resolution of D-loop Structures through Holliday Junction Intermediates / proteasome binding / Impaired BRCA2 binding to RAD51 / regulation of protein catabolic process / proteasome storage granule / Presynaptic phase of homologous DNA pairing and strand exchange / general transcription initiation factor binding / protein deubiquitination / blastocyst development / polyubiquitin modification-dependent protein binding / endopeptidase activator activity / proteasome assembly / mRNA export from nucleus / enzyme regulator activity / regulation of proteasomal protein catabolic process / inclusion body / TBP-class protein binding / proteasome complex / stem cell differentiation / Regulation of activated PAK-2p34 by proteasome mediated degradation / Autodegradation of Cdh1 by Cdh1:APC/C / APC/C:Cdc20 mediated degradation of Securin / ubiquitin binding / Asymmetric localization of PCP proteins / N-glycan trimming in the ER and Calnexin/Calreticulin cycle / Ubiquitin-dependent degradation of Cyclin D / SCF-beta-TrCP mediated degradation of Emi1 / NIK-->noncanonical NF-kB signaling / AUF1 (hnRNP D0) binds and destabilizes mRNA / TNFR2 non-canonical NF-kB pathway / P-body / Assembly of the pre-replicative complex / Vpu mediated degradation of CD4 / Cdc20:Phospho-APC/C mediated degradation of Cyclin A / Dectin-1 mediated noncanonical NF-kB signaling / Degradation of DVL / Degradation of CRY and PER proteins / Degradation of AXIN / Hh mutants are degraded by ERAD / Activation of NF-kappaB in B cells / G2/M Checkpoints / Degradation of GLI1 by the proteasome / Hedgehog ligand biogenesis / Autodegradation of the E3 ubiquitin ligase COP1 / Regulation of RUNX3 expression and activity / Defective CFTR causes cystic fibrosis / GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2 / Negative regulation of NOTCH4 signaling / Hedgehog 'on' state / APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1 / Vif-mediated degradation of APOBEC3G / FBXL7 down-regulates AURKA during mitotic entry and in early mitosis / Ubiquitin-Mediated Degradation of Phosphorylated Cdc25A / Degradation of GLI2 by the proteasome / GLI3 is processed to GLI3R by the proteasome / MAPK6/MAPK4 signaling / Degradation of CDH1 / double-strand break repair via homologous recombination / Degradation of beta-catenin by the destruction complex / Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha / double-strand break repair via nonhomologous end joining / HDR through Homologous Recombination (HRR) / ABC-family protein mediated transport / CDK-mediated phosphorylation and removal of Cdc6 / CLEC7A (Dectin-1) signaling / SCF(Skp2)-mediated degradation of p27/p21 / FCERI mediated NF-kB activation / Metalloprotease DUBs / Regulation of expression of SLITs and ROBOs / Regulation of PTEN stability and activity / Interleukin-1 signaling 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: 4.14 Å | |||||||||
データ登録者 | Zhu C / Qin L / Liang L | |||||||||
| 資金援助 | 中国, 1件
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引用 | ジャーナル: Nat Commun / 年: 2026タイトル: Structural dynamics of the midnolin-proteasome during ubiquitin-independent substrate turnover. 著者: Chuanda Zhu / Lu Qin / Zonglin Dai / Peng Zuo / Ao Yang / Lijun Zhong / Zhiqiang Lin / Ling Liang / ![]() 要旨: The 26S proteasome typically degrades proteins marked by ubiquitin chains. However, a distinct, ubiquitin-independent degradation pathway for nuclear proteins exists, mediated by the adaptor protein ...The 26S proteasome typically degrades proteins marked by ubiquitin chains. However, a distinct, ubiquitin-independent degradation pathway for nuclear proteins exists, mediated by the adaptor protein midnolin, yet its molecular mechanism remains poorly understood. Here, we present nine cryo-electron microscopy structures of the human 26S proteasome in complex with midnolin, which collectively delineate a near-complete catalytic cycle. Our structures reveal that midnolin binds to the proteasome via the RPN1 subunit by its C-terminal helix. Unexpectedly, its ubiquitin-like domain interacts with the RPN11 deubiquitinase in a non-catalytic role. This interaction positions the adjacent Catch domain, which is responsible for substrate binding, directly above the proteasomal entrance, potentially facilitating substrate entry into the proteasome. Furthermore, we observe four consecutive spiral staircase conformations of the AAA+ ATPase hexamer during substrate translocation. These findings provide insights into the mechanisms underlying ubiquitin-independent nuclear protein degradation and may help develop strategies for targeting nuclear proteins via direct proteasomal degradation. | |||||||||
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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_63850.map.gz | 168 MB | EMDBマップデータ形式 | |
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| ヘッダ (付随情報) | emd-63850-v30.xml emd-63850.xml | 41.1 KB 41.1 KB | 表示 表示 | EMDBヘッダ |
| FSC (解像度算出) | emd_63850_fsc.xml | 12 KB | 表示 | FSCデータファイル |
| 画像 | emd_63850.png | 61.8 KB | ||
| Filedesc metadata | emd-63850.cif.gz | 11.1 KB | ||
| その他 | emd_63850_half_map_1.map.gz emd_63850_half_map_2.map.gz | 165.3 MB 165.3 MB | ||
| アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-63850 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-63850 | HTTPS FTP |
-関連構造データ
| 関連構造データ | ![]() 9u4mMC ![]() 22mmC ![]() 9mboC ![]() 9mbpC ![]() 9mbqC ![]() 9u3lC ![]() 9u7rC ![]() 9w39C ![]() 9wbgC 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 ( |
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| 類似構造データ | 類似検索 - 機能・相同性 F&H 検索 |
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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_63850.map.gz / 形式: CCP4 / 大きさ: 178 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: 0.85 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
-ハーフマップ: #2
| ファイル | emd_63850_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_63850_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 |
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試料の構成要素
+全体 : 26S proteasome complexed with midnolin
+超分子 #1: 26S proteasome complexed with midnolin
+分子 #1: 26S proteasome non-ATPase regulatory subunit 6
+分子 #2: 26S proteasome non-ATPase regulatory subunit 13
+分子 #3: substrate peptide
+分子 #4: 26S proteasome regulatory subunit 4
+分子 #5: 26S proteasome non-ATPase regulatory subunit 14
+分子 #6: 26S proteasome non-ATPase regulatory subunit 7
+分子 #7: 26S proteasome complex subunit SEM1
+分子 #8: 26S proteasome non-ATPase regulatory subunit 1
+分子 #9: 26S proteasome non-ATPase regulatory subunit 12
+分子 #10: 26S proteasome regulatory subunit 7
+分子 #11: 26S proteasome regulatory subunit 8
+分子 #12: 26S proteasome regulatory subunit 6B
+分子 #13: Proteasome 26S subunit, ATPase 6
+分子 #14: 26S proteasome regulatory subunit 6A
+分子 #15: 26S proteasome non-ATPase regulatory subunit 11
+分子 #16: 26S proteasome non-ATPase regulatory subunit 3
+分子 #17: 26S proteasome non-ATPase regulatory subunit 8
+分子 #18: 26S proteasome non-ATPase regulatory subunit 4
+分子 #19: ADENOSINE-5'-DIPHOSPHATE
+分子 #20: ZINC ION
+分子 #21: ADENOSINE-5'-TRIPHOSPHATE
+分子 #22: MAGNESIUM ION
-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
| 緩衝液 | pH: 7.4 |
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| 凍結 | 凍結剤: ETHANE |
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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 (6k x 4k) / 平均電子線量: 40.0 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 / 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): 1.2 µm |
| 実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |
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)
データ登録者
中国, 1件
引用

































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

