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データを開く
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基本情報
登録情報 | データベース: PDB / ID: 8qys | |||||||||||||||
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タイトル | Human preholo proteasome 20S core particle | |||||||||||||||
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![]() | HYDROLASE / Complex | |||||||||||||||
機能・相同性 | ![]() cerebellar granule cell precursor proliferation / purine ribonucleoside triphosphate binding / protein folding chaperone complex / regulation of endopeptidase activity / proteasome core complex / Regulation of ornithine decarboxylase (ODC) / Cross-presentation of soluble exogenous antigens (endosomes) / proteasome core complex assembly / Somitogenesis / immune system process ...cerebellar granule cell precursor proliferation / purine ribonucleoside triphosphate binding / protein folding chaperone complex / regulation of endopeptidase activity / proteasome core complex / Regulation of ornithine decarboxylase (ODC) / Cross-presentation of soluble exogenous antigens (endosomes) / proteasome core complex assembly / Somitogenesis / immune system process / myofibril / proteasome binding / mitotic spindle assembly checkpoint signaling / NF-kappaB binding / proteasome assembly / chaperone-mediated protein complex assembly / proteasome endopeptidase complex / proteasome core complex, beta-subunit complex / proteasome core complex, alpha-subunit complex / threonine-type endopeptidase activity / negative regulation of inflammatory response to antigenic stimulus / response to organonitrogen compound / sarcomere / proteasome complex / Regulation of activated PAK-2p34 by proteasome mediated degradation / ciliary basal body / Autodegradation of Cdh1 by Cdh1:APC/C / APC/C:Cdc20 mediated degradation of Securin / proteolysis involved in protein catabolic process / Asymmetric localization of PCP proteins / SCF-beta-TrCP mediated degradation of Emi1 / AUF1 (hnRNP D0) binds and destabilizes mRNA / NIK-->noncanonical NF-kB signaling / Ubiquitin-dependent degradation of Cyclin D / TNFR2 non-canonical NF-kB pathway / Assembly of the pre-replicative complex / Vpu mediated degradation of CD4 / Degradation of DVL / 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 / Degradation of AXIN / lipopolysaccharide binding / Degradation of GLI1 by the proteasome / Activation of NF-kappaB in B cells / Defective CFTR causes cystic fibrosis / Hedgehog ligand biogenesis / 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 / FBXL7 down-regulates AURKA during mitotic entry and in early mitosis / MAPK6/MAPK4 signaling / P-body / APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1 / response to virus / Degradation of beta-catenin by the destruction complex / ABC-family proteins mediated transport / Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha / response to organic cyclic compound / CDK-mediated phosphorylation and removal of Cdc6 / CLEC7A (Dectin-1) signaling / SCF(Skp2)-mediated degradation of p27/p21 / Regulation of expression of SLITs and ROBOs / nuclear matrix / FCERI mediated NF-kB activation / Regulation of PTEN stability and activity / Interleukin-1 signaling / Orc1 removal from chromatin / Regulation of RAS by GAPs / Separation of Sister Chromatids / Regulation of RUNX2 expression and activity / UCH proteinases / The role of GTSE1 in G2/M progression after G2 checkpoint / KEAP1-NFE2L2 pathway / Antigen processing: Ubiquitination & Proteasome degradation / Downstream TCR signaling / RUNX1 regulates transcription of genes involved in differentiation of HSCs / Neddylation / positive regulation of NF-kappaB transcription factor activity / peptidase activity / ER-Phagosome pathway / regulation of inflammatory response / postsynapse / proteasome-mediated ubiquitin-dependent protein catabolic process / secretory granule lumen / endopeptidase activity / ficolin-1-rich granule lumen / response to oxidative stress / molecular adaptor activity / nuclear body / ribosome / Ub-specific processing proteases / nuclear speck 類似検索 - 分子機能 | |||||||||||||||
生物種 | ![]() | |||||||||||||||
手法 | 電子顕微鏡法 / 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3.89 Å | |||||||||||||||
![]() | Schulman, B.A. / Hanna, J.W. / Harper, J.W. / Adolf, F. / Du, J. / Rawson, S.D. / Walsh Jr, R.M. / Goodall, E.A. | |||||||||||||||
資金援助 | ![]() ![]()
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![]() | ![]() タイトル: Visualizing chaperone-mediated multistep assembly of the human 20S proteasome. 著者: Frank Adolf / Jiale Du / Ellen A Goodall / Richard M Walsh / Shaun Rawson / Susanne von Gronau / J Wade Harper / John Hanna / Brenda A Schulman / ![]() ![]() 要旨: Dedicated assembly factors orchestrate the stepwise production of many molecular machines, including the 28-subunit proteasome core particle (CP) that mediates protein degradation. Here we report ...Dedicated assembly factors orchestrate the stepwise production of many molecular machines, including the 28-subunit proteasome core particle (CP) that mediates protein degradation. Here we report cryo-electron microscopy reconstructions of seven recombinant human subcomplexes that visualize all five chaperones and the three active site propeptides across a wide swath of the assembly pathway. Comparison of these chaperone-bound intermediates and a matching mature CP reveals molecular mechanisms determining the order of successive subunit additions, as well as how proteasome subcomplexes and assembly factors structurally adapt upon progressive subunit incorporation to stabilize intermediates, facilitate the formation of subsequent intermediates and ultimately rearrange to coordinate proteolytic activation with gated access to active sites. This work establishes a methodologic approach for structural analysis of multiprotein complex assembly intermediates, illuminates specific functions of assembly factors and reveals conceptual principles underlying human proteasome biogenesis, thus providing an explanation for many previous biochemical and genetic observations. #1: ジャーナル: bioRxiv / 年: 2024 タイトル: Visualizing chaperone-mediated multistep assembly of the human 20S proteasome. 著者: Frank Adolf / Jiale Du / Ellen A Goodall / Richard M Walsh / Shaun Rawson / Susanne von Gronau / J Wade Harper / John Hanna / Brenda A Schulman / ![]() ![]() 要旨: Dedicated assembly factors orchestrate stepwise production of many molecular machines, including the 28-subunit proteasome core particle (CP) that mediates protein degradation. Here, we report cryo- ...Dedicated assembly factors orchestrate stepwise production of many molecular machines, including the 28-subunit proteasome core particle (CP) that mediates protein degradation. Here, we report cryo-EM reconstructions of seven recombinant human subcomplexes that visualize all five chaperones and the three active site propeptides across a wide swath of the assembly pathway. Comparison of these chaperone-bound intermediates and a matching mature CP reveals molecular mechanisms determining the order of successive subunit additions, and how proteasome subcomplexes and assembly factors structurally adapt upon progressive subunit incorporation to stabilize intermediates, facilitate the formation of subsequent intermediates, and ultimately rearrange to coordinate proteolytic activation with gated access to active sites. The structural findings reported here explain many previous biochemical and genetic observations. This work establishes a methodologic approach for structural analysis of multiprotein complex assembly intermediates, illuminates specific functions of assembly factors, and reveals conceptual principles underlying human proteasome biogenesis. | |||||||||||||||
履歴 |
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構造の表示
構造ビューア | 分子: ![]() ![]() |
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ダウンロードとリンク
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ダウンロード
PDBx/mmCIF形式 | ![]() | 1.2 MB | 表示 | ![]() |
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PDB形式 | ![]() | 1 MB | 表示 | ![]() |
PDBx/mmJSON形式 | ![]() | ツリー表示 | ![]() | |
その他 | ![]() |
-検証レポート
文書・要旨 | ![]() | 1.3 MB | 表示 | ![]() |
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文書・詳細版 | ![]() | 1.3 MB | 表示 | |
XML形式データ | ![]() | 164.1 KB | 表示 | |
CIF形式データ | ![]() | 265.4 KB | 表示 | |
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-関連構造データ
関連構造データ | ![]() 18761MC ![]() 8qyjC ![]() 8qylC ![]() 8qymC ![]() 8qynC ![]() 8qyoC ![]() 8qz9C M: このデータのモデリングに利用したマップデータ 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 ![]() |
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リンク
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集合体
登録構造単位 | ![]()
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要素
-Proteasome subunit alpha type- ... , 7種, 14分子 ARBSCTDUEVFWGX
#1: タンパク質 | 分子量: 25927.535 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() #2: タンパク質 | 分子量: 27901.932 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() #3: タンパク質 | 分子量: 26277.986 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() #4: タンパク質 | 分子量: 26322.818 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() #5: タンパク質 | 分子量: 27163.992 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() #6: タンパク質 | 分子量: 26870.670 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() #7: タンパク質 | 分子量: 27160.178 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() |
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-タンパク質 , 1種, 2分子 HY
#8: タンパク質 | 分子量: 15804.993 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() |
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-Proteasome assembly chaperone ... , 2種, 4分子 IZJa
#9: タンパク質 | 分子量: 32891.887 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() #10: タンパク質 | 分子量: 29423.041 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() |
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-Proteasome subunit beta type- ... , 7種, 14分子 KbLcMdNeOfPgQh
#11: タンパク質 | 分子量: 28292.514 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() #12: タンパク質 | 分子量: 22754.623 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() #13: タンパク質 | 分子量: 22462.838 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() #14: タンパク質 | 分子量: 22978.012 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() #15: タンパク質 | 分子量: 23421.793 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() #16: タンパク質 | 分子量: 23159.316 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() #17: タンパク質 | 分子量: 21158.898 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() |
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-実験情報
-実験
実験 | 手法: 電子顕微鏡法 |
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EM実験 | 試料の集合状態: PARTICLE / 3次元再構成法: 単粒子再構成法 |
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試料調製
構成要素 | 名称: Human preholo proteasome 20S core particle / タイプ: COMPLEX / Entity ID: all / 由来: RECOMBINANT |
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由来(天然) | 生物種: ![]() |
由来(組換発現) | 生物種: ![]() |
緩衝液 | pH: 7.5 |
試料 | 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES |
急速凍結 | 凍結剤: ETHANE-PROPANE |
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電子顕微鏡撮影
顕微鏡 | モデル: TFS GLACIOS |
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電子銃 | 電子線源: ![]() |
電子レンズ | モード: BRIGHT FIELD / 最大 デフォーカス(公称値): 2600 nm / 最小 デフォーカス(公称値): 1000 nm |
撮影 | 電子線照射量: 60 e/Å2 フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) |
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解析
CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
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3次元再構成 | 解像度: 3.89 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 59535 / 対称性のタイプ: POINT | ||||||||||||||||||||||||
拘束条件 |
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