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基本情報
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タイトル | Structure of human substrate-free 26S proteasome in the presence of ATPgS and MG-132,SA-like state (composite map) | |||||||||
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![]() | Apo state / proteasome / Midnolin / substrate-free 26S / MG-132 / IMMUNE SYSTEM | |||||||||
機能・相同性 | ![]() thyrotropin-releasing hormone receptor binding / nuclear proteasome complex / host-mediated perturbation of viral transcription / Impaired BRCA2 translocation to the nucleus / Impaired BRCA2 binding to SEM1 (DSS1) / positive regulation of inclusion body assembly / 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 ...thyrotropin-releasing hormone receptor binding / nuclear proteasome complex / host-mediated perturbation of viral transcription / Impaired BRCA2 translocation to the nucleus / Impaired BRCA2 binding to SEM1 (DSS1) / positive regulation of inclusion body assembly / 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 / 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 / metal-dependent deubiquitinase activity / negative regulation of programmed cell death / protein K63-linked deubiquitination / Regulation of ornithine decarboxylase (ODC) / Proteasome assembly / Cross-presentation of soluble exogenous antigens (endosomes) / 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) / proteasome core complex / Resolution of D-loop Structures through Holliday Junction Intermediates / Somitogenesis / K63-linked deubiquitinase activity / Impaired BRCA2 binding to RAD51 / proteasome binding / transcription factor binding / regulation of protein catabolic process / myofibril / proteasome storage granule / Presynaptic phase of homologous DNA pairing and strand exchange / general transcription initiation factor binding / blastocyst development / polyubiquitin modification-dependent protein binding / protein deubiquitination / regulation of proteasomal protein catabolic process / NF-kappaB binding / proteasome endopeptidase complex / endopeptidase activator activity / proteasome core complex, beta-subunit complex / proteasome assembly / threonine-type endopeptidase activity / proteasome core complex, alpha-subunit complex / mRNA export from nucleus / enzyme regulator activity / immune system process / inclusion body / Regulation of activated PAK-2p34 by proteasome mediated degradation / Autodegradation of Cdh1 by Cdh1:APC/C / N-glycan trimming in the ER and Calnexin/Calreticulin cycle / APC/C:Cdc20 mediated degradation of Securin / Asymmetric localization of PCP proteins / Ubiquitin-dependent degradation of Cyclin D / NIK-->noncanonical NF-kB signaling / SCF-beta-TrCP mediated degradation of Emi1 / proteasome complex / proteolysis involved in protein catabolic process / TNFR2 non-canonical NF-kB pathway / AUF1 (hnRNP D0) binds and destabilizes mRNA / TBP-class protein binding / Vpu mediated degradation of CD4 / Assembly of the pre-replicative complex / Ubiquitin-Mediated Degradation of Phosphorylated Cdc25A / Degradation of DVL / Dectin-1 mediated noncanonical NF-kB signaling / sarcomere / Cdc20:Phospho-APC/C mediated degradation of Cyclin A / Degradation of AXIN / Hh mutants are degraded by ERAD / Activation of NF-kappaB in B cells / Degradation of GLI1 by the proteasome / Hedgehog ligand biogenesis / G2/M Checkpoints / Defective CFTR causes cystic fibrosis / GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2 / Autodegradation of the E3 ubiquitin ligase COP1 / Negative regulation of NOTCH4 signaling / Vif-mediated degradation of APOBEC3G / Regulation of RUNX3 expression and activity / Hedgehog 'on' state / double-strand break repair via homologous recombination / Degradation of GLI2 by the proteasome / GLI3 is processed to GLI3R by the proteasome / FBXL7 down-regulates AURKA during mitotic entry and in early mitosis / APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1 / MAPK6/MAPK4 signaling / stem cell differentiation / Degradation of beta-catenin by the destruction complex / lipopolysaccharide binding / negative regulation of inflammatory response to antigenic stimulus / ABC-family proteins mediated transport / P-body 類似検索 - 分子機能 | |||||||||
生物種 | ![]() | |||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 2.9 Å | |||||||||
![]() | Peddada N / Beutler B | |||||||||
資金援助 | ![]()
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![]() | ![]() タイトル: Structural insights into the ubiquitin-independent midnolin-proteasome pathway. 著者: Nagesh Peddada / Xue Zhong / Yan Yin / Danielle Renee Lazaro / Jianhui Wang / Stephen Lyon / Jin Huk Choi / Xiao-Chen Bai / Eva Marie Y Moresco / Bruce Beutler / ![]() 要旨: The protein midnolin (MIDN) augments proteasome activity in lymphocytes and dramatically facilitates the survival and proliferation of B-lymphoid malignancies. MIDN binds both to proteasomes and to ...The protein midnolin (MIDN) augments proteasome activity in lymphocytes and dramatically facilitates the survival and proliferation of B-lymphoid malignancies. MIDN binds both to proteasomes and to substrates, but the mode of interaction with the proteasome is unknown, and the mechanism by which MIDN facilitates substrate degradation in a ubiquitin-independent manner is incompletely understood. Here, we present cryoelectron microscopy (cryo-EM) structures of the substrate-engaged, MIDN-bound human proteasome in two conformational states. MIDN induces proteasome conformations similarly to ubiquitinated substrates by using its ubiquitin-like domain to bind to the deubiquitinase RPN11 (PSMD14). By simultaneously binding to RPN1 (PSMD2) with its C-terminal α-helix, MIDN positions its substrate-carrying Catch domain above the proteasome ATPase channel through which substrates are translocated before degradation. Our findings suggest that both ubiquitin-like domain and C-terminal α-helix must bind to the proteasome for MIDN to stimulate proteasome activity. | |||||||||
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「今月の分子」の関連する項目 |
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ファイル | ![]() | ||||||||||||||||||||||||||||||||||||
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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 これらの図は立方格子座標系で作成されたものです | ||||||||||||||||||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 1.074 Å | ||||||||||||||||||||||||||||||||||||
密度 |
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対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||
詳細 | EMDB XML:
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試料の構成要素
+全体 : Structure of Substrate-free human 26S proteasome in presence of M...
+超分子 #1: Structure of Substrate-free human 26S proteasome in presence of M...
+分子 #1: 26S proteasome regulatory subunit 7
+分子 #2: 26S proteasome regulatory subunit 4
+分子 #3: 26S protease regulatory subunit 8
+分子 #4: 26S proteasome regulatory subunit 6B
+分子 #5: 26S proteasome regulatory subunit 10B
+分子 #6: Proteasome subunit alpha type-6
+分子 #7: Proteasome subunit alpha type-2
+分子 #8: Proteasome subunit alpha type-4
+分子 #9: Proteasome subunit alpha type-7
+分子 #10: Proteasome subunit alpha type-5
+分子 #11: Proteasome subunit alpha type-1
+分子 #12: Proteasome subunit alpha type-3
+分子 #13: Proteasome subunit beta type-6
+分子 #14: Proteasome subunit beta type-7
+分子 #15: Proteasome subunit beta type-3
+分子 #16: Proteasome subunit beta type-2
+分子 #17: Proteasome subunit beta type-5
+分子 #18: Proteasome subunit beta type-1
+分子 #19: Proteasome subunit beta type-4
+分子 #20: 26S proteasome non-ATPase regulatory subunit 3
+分子 #21: 26S proteasome non-ATPase regulatory subunit 12
+分子 #22: 26S proteasome non-ATPase regulatory subunit 11
+分子 #23: 26S proteasome non-ATPase regulatory subunit 6
+分子 #24: 26S proteasome non-ATPase regulatory subunit 7
+分子 #25: 26S proteasome non-ATPase regulatory subunit 13
+分子 #26: 26S proteasome non-ATPase regulatory subunit 4
+分子 #27: 26S proteasome non-ATPase regulatory subunit 14
+分子 #28: 26S proteasome non-ATPase regulatory subunit 8
+分子 #29: 26S proteasome complex subunit SEM1
+分子 #30: 26S proteasome non-ATPase regulatory subunit 2
+分子 #31: 26S proteasome regulatory subunit 6A
+分子 #32: 26S proteasome non-ATPase regulatory subunit 1
+分子 #33: ADENOSINE-5'-TRIPHOSPHATE
+分子 #34: MAGNESIUM ION
+分子 #35: ADENOSINE-5'-DIPHOSPHATE
+分子 #36: N-[(benzyloxy)carbonyl]-L-leucyl-N-[(2S)-4-methyl-1-oxopentan-2-y...
+分子 #37: ZINC 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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![]() | 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: 7.6 詳細: 50 mM Tris, pH 7.5, 150 mM NaCl, 20 mM KCl,5 mM MgCl2, 1 mM TECP, |
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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 |
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電子顕微鏡法
顕微鏡 | TFS KRIOS |
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特殊光学系 | エネルギーフィルター - 名称: GIF Bioquantum |
撮影 | フィルム・検出器のモデル: GATAN K3 BIOQUANTUM (6k x 4k) 撮影したグリッド数: 1 / 実像数: 13162 / 平均電子線量: 50.0 e/Å2 |
電子線 | 加速電圧: 300 kV / 電子線源: ![]() |
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): 2.7 µm / 最小 デフォーカス(公称値): 1.1 µm / 倍率(公称値): 81000 |
試料ステージ | 試料ホルダーモデル: FEI TITAN KRIOS AUTOGRID HOLDER |
実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |