+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 7mhs | |||||||||
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タイトル | Structure of p97 (subunits A to E) with substrate engaged | |||||||||
要素 |
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キーワード | HYDROLASE / p97 / VCP / AAA+ ATPase / peptide translocation | |||||||||
機能・相同性 | 機能・相同性情報 positive regulation of Lys63-specific deubiquitinase activity / flavin adenine dinucleotide catabolic process / positive regulation of oxidative phosphorylation / VCP-NSFL1C complex / cytoplasm protein quality control / endosome to lysosome transport via multivesicular body sorting pathway / endoplasmic reticulum stress-induced pre-emptive quality control / cellular response to arsenite ion / Derlin-1 retrotranslocation complex / BAT3 complex binding ...positive regulation of Lys63-specific deubiquitinase activity / flavin adenine dinucleotide catabolic process / positive regulation of oxidative phosphorylation / VCP-NSFL1C complex / cytoplasm protein quality control / endosome to lysosome transport via multivesicular body sorting pathway / endoplasmic reticulum stress-induced pre-emptive quality control / cellular response to arsenite ion / Derlin-1 retrotranslocation complex / BAT3 complex binding / protein-DNA covalent cross-linking repair / positive regulation of protein K63-linked deubiquitination / deubiquitinase activator activity / mitotic spindle disassembly / VCP-NPL4-UFD1 AAA ATPase complex / ubiquitin-modified protein reader activity / regulation of protein localization to chromatin / aggresome assembly / vesicle-fusing ATPase / NADH metabolic process / cellular response to misfolded protein / stress granule disassembly / negative regulation of protein localization to chromatin / positive regulation of mitochondrial membrane potential / retrograde protein transport, ER to cytosol / K48-linked polyubiquitin modification-dependent protein binding / regulation of aerobic respiration / regulation of synapse organization / positive regulation of ATP biosynthetic process / ubiquitin-specific protease binding / ATPase complex / MHC class I protein binding / ubiquitin-like protein ligase binding / RHOH GTPase cycle / polyubiquitin modification-dependent protein binding / autophagosome maturation / HSF1 activation / negative regulation of hippo signaling / endoplasmic reticulum to Golgi vesicle-mediated transport / proteasomal protein catabolic process / translesion synthesis / Protein methylation / interstrand cross-link repair / ATP metabolic process / negative regulation of smoothened signaling pathway / ERAD pathway / endoplasmic reticulum unfolded protein response / Attachment and Entry / proteasome complex / viral genome replication / lipid droplet / Josephin domain DUBs / N-glycan trimming in the ER and Calnexin/Calreticulin cycle / macroautophagy / Hh mutants are degraded by ERAD / Hedgehog ligand biogenesis / Defective CFTR causes cystic fibrosis / positive regulation of protein-containing complex assembly / ADP binding / Translesion Synthesis by POLH / establishment of protein localization / ABC-family proteins mediated transport / : / autophagy / Aggrephagy / cytoplasmic stress granule / positive regulation of non-canonical NF-kappaB signal transduction / positive regulation of protein catabolic process / azurophil granule lumen / KEAP1-NFE2L2 pathway / positive regulation of canonical Wnt signaling pathway / double-strand break repair / Ovarian tumor domain proteases / positive regulation of proteasomal ubiquitin-dependent protein catabolic process / E3 ubiquitin ligases ubiquitinate target proteins / site of double-strand break / Neddylation / cellular response to heat / ubiquitin-dependent protein catabolic process / protein phosphatase binding / secretory granule lumen / regulation of apoptotic process / proteasome-mediated ubiquitin-dependent protein catabolic process / ficolin-1-rich granule lumen / Attachment and Entry / protein ubiquitination / protein domain specific binding / intracellular membrane-bounded organelle / DNA repair / lipid binding / glutamatergic synapse / DNA damage response / ubiquitin protein ligase binding / Neutrophil degranulation / endoplasmic reticulum membrane / perinuclear region of cytoplasm / endoplasmic reticulum / ATP hydrolysis activity / protein-containing complex / 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: 3.6 Å | |||||||||
データ登録者 | Xu, Y. / Han, H. / Cooney, I. / Hill, C.P. / Shen, P.S. | |||||||||
資金援助 | 米国, 2件
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引用 | ジャーナル: Nat Commun / 年: 2022 タイトル: Active conformation of the p97-p47 unfoldase complex. 著者: Yang Xu / Han Han / Ian Cooney / Yuxuan Guo / Noah G Moran / Nathan R Zuniga / John C Price / Christopher P Hill / Peter S Shen / 要旨: The p97 AAA+ATPase is an essential and abundant regulator of protein homeostasis that plays a central role in unfolding ubiquitylated substrates. Here we report two cryo-EM structures of human p97 in ...The p97 AAA+ATPase is an essential and abundant regulator of protein homeostasis that plays a central role in unfolding ubiquitylated substrates. Here we report two cryo-EM structures of human p97 in complex with its p47 adaptor. One of the conformations is six-fold symmetric, corresponds to previously reported structures of p97, and lacks bound substrate. The other structure adopts a helical conformation, displays substrate running in an extended conformation through the pore of the p97 hexamer, and resembles structures reported for other AAA unfoldases. These findings support the model that p97 utilizes a "hand-over-hand" mechanism in which two residues of the substrate are translocated for hydrolysis of two ATPs, one in each of the two p97 AAA ATPase rings. Proteomics analysis supports the model that one p97 complex can bind multiple substrate adaptors or binding partners, and can process substrates with multiple types of ubiquitin modification. | |||||||||
履歴 |
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-構造の表示
構造ビューア | 分子: MolmilJmol/JSmol |
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-ダウンロードとリンク
-ダウンロード
PDBx/mmCIF形式 | 7mhs.cif.gz | 473.5 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb7mhs.ent.gz | 386.8 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 7mhs.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 | 7mhs_validation.pdf.gz | 1.5 MB | 表示 | wwPDB検証レポート |
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文書・詳細版 | 7mhs_full_validation.pdf.gz | 1.5 MB | 表示 | |
XML形式データ | 7mhs_validation.xml.gz | 72.8 KB | 表示 | |
CIF形式データ | 7mhs_validation.cif.gz | 108.3 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/mh/7mhs ftp://data.pdbj.org/pub/pdb/validation_reports/mh/7mhs | HTTPS FTP |
-関連構造データ
関連構造データ | 23835MC 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 | 類似検索 - 機能・相同性F&H 検索 |
-リンク
-集合体
登録構造単位 |
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1 |
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-要素
#1: タンパク質 | 分子量: 89436.820 Da / 分子数: 5 / 由来タイプ: 天然 / 由来: (天然) Homo sapiens (ヒト) / 参照: UniProt: P55072, vesicle-fusing ATPase #2: タンパク質・ペプチド | | 分子量: 1890.321 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Homo sapiens (ヒト) #3: 化合物 | ChemComp-ADP / #4: 化合物 | ChemComp-BEF / #5: 化合物 | ChemComp-MG / 研究の焦点であるリガンドがあるか | N | 配列の詳細 | Unknown substrate modeled as AAAAAAAAAA | |
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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: p97 hexamer with substrate engaged / タイプ: COMPLEX / Entity ID: #1-#2 / 由来: NATURAL |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
緩衝液 | pH: 7.4 |
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: Titan Krios / 画像提供: FEI Company |
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顕微鏡 | モデル: FEI TITAN KRIOS |
電子銃 | 電子線源: FIELD EMISSION GUN / 加速電圧: 300 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: 46 e/Å2 / フィルム・検出器のモデル: GATAN K3 (6k x 4k) |
-解析
ソフトウェア |
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CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | |||||||||
3次元再構成 | 解像度: 3.6 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 85965 / 対称性のタイプ: POINT | |||||||||
精密化 | 最高解像度: 3.6 Å / 交差検証法: NONE |