+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 5vfo | ||||||
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タイトル | Nucleotide-driven Triple-state Remodeling of the AAA-ATPase Channel in the Activated Human 26S Proteasome | ||||||
要素 |
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キーワード | HYDROLASE / 26S proteasome / ATP-dependent protease / AAA-ATPase / peptide-unfolding channel / 20S core particle | ||||||
機能・相同性 | 機能・相同性情報 purine ribonucleoside triphosphate binding / regulation of endopeptidase activity / Regulation of ornithine decarboxylase (ODC) / proteasome core complex / Cross-presentation of soluble exogenous antigens (endosomes) / Somitogenesis / immune system process / myofibril / NF-kappaB binding / proteasome endopeptidase complex ...purine ribonucleoside triphosphate binding / regulation of endopeptidase activity / Regulation of ornithine decarboxylase (ODC) / proteasome core complex / Cross-presentation of soluble exogenous antigens (endosomes) / Somitogenesis / immune system process / myofibril / NF-kappaB binding / 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 / : / sarcomere / proteasome complex / Regulation of activated PAK-2p34 by proteasome mediated degradation / ciliary basal body / 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 / Vpu mediated degradation of CD4 / Assembly of the pre-replicative complex / Degradation of DVL / CDK-mediated phosphorylation and removal of Cdc6 / 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 / SCF(Skp2)-mediated degradation of p27/p21 / 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 / P-body / Degradation of GLI2 by the proteasome / GLI3 is processed to GLI3R by the proteasome / Orc1 removal from chromatin / FBXL7 down-regulates AURKA during mitotic entry and in early mitosis / MAPK6/MAPK4 signaling / 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 / CLEC7A (Dectin-1) signaling / Regulation of expression of SLITs and ROBOs / FCERI mediated NF-kB activation / nuclear matrix / Regulation of PTEN stability and activity / Interleukin-1 signaling / Regulation of RAS by GAPs / Separation of Sister Chromatids / Regulation of RUNX2 expression and activity / The role of GTSE1 in G2/M progression after G2 checkpoint / UCH proteinases / KEAP1-NFE2L2 pathway / Antigen processing: Ubiquitination & Proteasome degradation / regulation of inflammatory response / 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 / endopeptidase activity / proteasome-mediated ubiquitin-dependent protein catabolic process / secretory granule lumen / response to oxidative stress / ficolin-1-rich granule lumen / postsynapse / nuclear body / ribosome / Ub-specific processing proteases / cadherin binding / intracellular membrane-bounded organelle / centrosome / ubiquitin protein ligase binding / synapse / Neutrophil degranulation / mitochondrion / proteolysis / RNA binding 類似検索 - 分子機能 | ||||||
生物種 | Homo sapiens (ヒト) | ||||||
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: 3.5 Å | ||||||
データ登録者 | Zhu, Y. / Wang, W.L. / Yu, D. / Ouyang, Q. / Lu, Y. / Mao, Y. | ||||||
引用 | ジャーナル: Nat Commun / 年: 2018 タイトル: Structural mechanism for nucleotide-driven remodeling of the AAA-ATPase unfoldase in the activated human 26S proteasome. 著者: Yanan Zhu / Wei Li Wang / Daqi Yu / Qi Ouyang / Ying Lu / Youdong Mao / 要旨: The proteasome is a sophisticated ATP-dependent molecular machine responsible for protein degradation in all known eukaryotic cells. It remains elusive how conformational changes of the AAA-ATPase ...The proteasome is a sophisticated ATP-dependent molecular machine responsible for protein degradation in all known eukaryotic cells. It remains elusive how conformational changes of the AAA-ATPase unfoldase in the regulatory particle (RP) control the gating of the substrate-translocation channel leading to the proteolytic chamber of the core particle (CP). Here we report three alternative states of the ATP-γ-S-bound human proteasome, in which the CP gates are asymmetrically open, visualized by cryo-EM at near-atomic resolutions. At least four nucleotides are bound to the AAA-ATPase ring in these open-gate states. Variation in nucleotide binding gives rise to an axial movement of the pore loops narrowing the substrate-translation channel, which exhibit remarkable structural transitions between the spiral-staircase and saddle-shaped-circle topologies. Gate opening in the CP is thus regulated by nucleotide-driven conformational changes of the AAA-ATPase unfoldase. These findings demonstrate an elegant mechanism of allosteric coordination among sub-machines within the human proteasome holoenzyme. | ||||||
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 | 分子: MolmilJmol/JSmol |
-ダウンロードとリンク
-ダウンロード
PDBx/mmCIF形式 | 5vfo.cif.gz | 1.4 MB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb5vfo.ent.gz | 1.1 MB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 5vfo.json.gz | ツリー表示 | PDBx/mmJSON形式 | |
その他 | その他のダウンロード |
-検証レポート
文書・要旨 | 5vfo_validation.pdf.gz | 1.1 MB | 表示 | wwPDB検証レポート |
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文書・詳細版 | 5vfo_full_validation.pdf.gz | 1.1 MB | 表示 | |
XML形式データ | 5vfo_validation.xml.gz | 139.8 KB | 表示 | |
CIF形式データ | 5vfo_validation.cif.gz | 224.2 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/vf/5vfo ftp://data.pdbj.org/pub/pdb/validation_reports/vf/5vfo | HTTPS FTP |
-関連構造データ
関連構造データ | 8662MC 8663C 8664C 8665C 8666C 8667C 8668C 5vfpC 5vfqC 5vfrC 5vfsC 5vftC 5vfuC 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 (文献) |
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類似構造データ | |
電子顕微鏡画像生データ | EMPIAR-10090 (タイトル: Nucleotide-Driven Triple-State Remodeling of the AAA-ATPase Channel in the Activated Human 26S Proteasome Data size: 2.8 TB Data #1: Motion-corrected single frame micrographs of ATP-gS-bound human proteasome [micrographs - single frame] Data #2: Single-particle stacks of classified conformations [picked particles - multiframe - processed]) |
-リンク
-集合体
登録構造単位 |
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-要素
-Proteasome subunit alpha type- ... , 7種, 14分子 GgHhIiJjKkLlMm
#1: タンパク質 | 分子量: 26727.658 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: PSMA6, PROS27 / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: P60900, proteasome endopeptidase complex #2: タンパク質 | 分子量: 25725.260 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: PSMA2, HC3, PSC3 / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: P25787, proteasome endopeptidase complex #3: タンパク質 | 分子量: 28118.189 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: PSMA4, HC9, PSC9 / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: P25789, proteasome endopeptidase complex #4: タンパク質 | 分子量: 27382.178 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: PSMA7, HSPC / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: O14818, proteasome endopeptidase complex #5: タンパク質 | 分子量: 25569.957 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: PSMA5 / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: P28066, proteasome endopeptidase complex #6: タンパク質 | 分子量: 26728.428 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: PSMA1, HC2, NU, PROS30, PSC2 / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: P25786, proteasome endopeptidase complex #7: タンパク質 | 分子量: 27287.100 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: PSMA3, HC8, PSC8 / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: P25788, proteasome endopeptidase complex |
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-Proteasome subunit beta type- ... , 7種, 14分子 NnOoPpQqRrSsTt
#8: タンパク質 | 分子量: 20471.129 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: PSMB6, LMPY, Y / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: P28072, proteasome endopeptidase complex #9: タンパク質 | 分子量: 23745.256 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: PSMB7, Z / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: Q99436, proteasome endopeptidase complex #10: タンパク質 | 分子量: 22841.701 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: PSMB3 / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: P49720, proteasome endopeptidase complex #11: タンパク質 | 分子量: 22720.146 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: PSMB2 / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: P49721, proteasome endopeptidase complex #12: タンパク質 | 分子量: 22199.072 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: PSMB5, LMPX, MB1, X / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: P28074, proteasome endopeptidase complex #13: タンパク質 | 分子量: 23578.986 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: PSMB1, PSC5 / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: P20618, proteasome endopeptidase complex #14: タンパク質 | 分子量: 23994.324 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: PSMB4, PROS26 / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: P28070, proteasome endopeptidase complex |
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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 |
-試料調製
構成要素 | 名称: 26S proteasome bound to ATP-gammaS / タイプ: COMPLEX / Entity ID: all / 由来: RECOMBINANT |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
由来(組換発現) | 生物種: Homo sapiens (ヒト) |
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 |
-電子顕微鏡撮影
実験機器 | モデル: Talos Arctica / 画像提供: FEI Company |
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顕微鏡 | モデル: FEI TECNAI ARCTICA |
電子銃 | 電子線源: FIELD EMISSION GUN / 加速電圧: 200 kV / 照射モード: FLOOD BEAM |
電子レンズ | モード: BRIGHT FIELD |
撮影 | 電子線照射量: 30 e/Å2 フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) |
-解析
ソフトウェア | 名称: PHENIX / バージョン: 1.11.1_2575: / 分類: 精密化 | ||||||||||||||||||||||||
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CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
対称性 | 点対称性: C1 (非対称) | ||||||||||||||||||||||||
3次元再構成 | 解像度: 3.5 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 228086 / 対称性のタイプ: POINT | ||||||||||||||||||||||||
拘束条件 |
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