EMDB/PDB/SASBDBから引用されている文献のデータベース

キーワード
構造解析手法	All X線回折 NMR 電子顕微鏡小角散乱中性子線回折線維回折粉末回折赤外分光 EPR FRET 理論モデルハイブリッド
著者・登録者
ジャーナル
IF	>30 >20 >10 >5 all

タイトル	Mechanistic insight into substrate processing and allosteric inhibition of human p97.
ジャーナル・号・ページ	Nat Struct Mol Biol, Vol. 28, Issue 7, Page 614-625, Year 2021
掲載日	2021年7月14日
著者	Man Pan / Yuanyuan Yu / Huasong Ai / Qingyun Zheng / Yuan Xie / Lei Liu / Minglei Zhao /
PubMed 要旨	p97 processes ubiquitinated substrates and plays a central role in cellular protein homeostasis. Here, we report a series of cryo-EM structures of the substrate-engaged human p97 complex with ...p97 processes ubiquitinated substrates and plays a central role in cellular protein homeostasis. Here, we report a series of cryo-EM structures of the substrate-engaged human p97 complex with resolutions ranging from 2.9 to 3.8 Å that captured 'power-stroke'-like motions of both the D1 and D2 ATPase rings of p97. A key feature of these structures is the critical conformational changes of the intersubunit signaling (ISS) motifs, which tighten the binding of nucleotides and neighboring subunits and contribute to the spiral staircase conformation of the D1 and D2 rings. In addition, we determined the cryo-EM structure of human p97 in complex with NMS-873, a potent p97 inhibitor, at a resolution of 2.4 Å. The structures showed that NMS-873 binds at a cryptic groove in the D2 domain and interacts with the ISS motif, preventing its conformational change and thus blocking substrate translocation allosterically.
リンク	Nat Struct Mol Biol / PubMed:34262183
手法	EM (単粒子)
解像度	2.4 - 6.0 Å
構造データ	23442 7lmy EMDB-23442, PDB-7lmy: Cryo-EM structure of human p97 in complex with NMS-873 in the presence of ATP, Npl4/Ufd1, and Ub6 手法: EM (単粒子) / 解像度: 2.4 Å 23443 7lmz EMDB-23443, PDB-7lmz: Cryo-EM structure of human p97 in complex with Npl4/Ufd1 and Ub6 (Class 1) 手法: EM (単粒子) / 解像度: 3.06 Å 23444 7ln0 EMDB-23444, PDB-7ln0: Cryo-EM structure of human p97 in complex with Npl4/Ufd1 and Ub6 (Class 2) 手法: EM (単粒子) / 解像度: 2.98 Å 23445 7ln1 EMDB-23445, PDB-7ln1: Cryo-EM structure of human p97 in complex with Npl4/Ufd1 and Ub6 (Class 3) 手法: EM (単粒子) / 解像度: 3.4 Å 23446 7ln2 EMDB-23446, PDB-7ln2: Cryo-EM structure of human p97 in complex with Npl4/Ufd1 and polyubiquitinated Ub-Eos (FOM, Class 1) 手法: EM (単粒子) / 解像度: 3.63 Å 23447 7ln3 EMDB-23447, PDB-7ln3: Cryo-EM structure of human p97 in complex with Npl4/Ufd1 and polyubiquitinated Ub-Eos (FOM, Class 2) 手法: EM (単粒子) / 解像度: 3.45 Å 23448 7ln4 EMDB-23448, PDB-7ln4: Cryo-EM structure of human p97 in complex with Npl4/Ufd1 and polyubiquitinated Ub-Eos (FOM, Class 3) 手法: EM (単粒子) / 解像度: 3.0 Å 23449 7ln5 EMDB-23449, PDB-7ln5: Cryo-EM structure of human p97 in complex with Npl4/Ufd1 and polyubiquitinated Ub-Eos (CHAPSO, Class 1, Close State) 手法: EM (単粒子) / 解像度: 3.09 Å 23450 7ln6 EMDB-23450, PDB-7ln6: Cryo-EM structure of human p97 in complex with Npl4/Ufd1 and polyubiquitinated Ub-Eos (CHAPSO, Class 2, Open State) 手法: EM (単粒子) / 解像度: 3.58 Å EMDB-23451: Human p97 in complex with Npl4/Ufd1 and polyubiquitinated Ub-Eos (Class 3) 手法: EM (単粒子) / 解像度: 3.77 Å EMDB-23452: Human p97 in complex with NMS-873 in the presence of ATP, Npl4/Ufd1 and plyubiquitinated Ub-Eos 手法: EM (単粒子) / 解像度: 2.87 Å EMDB-23453: Human p97 in complex with Npl4/Ufd1 and polyubiquitinated Ub-Eos in the presence of ATP and sub-stoichiometric NMS-873 (Class 1) 手法: EM (単粒子) / 解像度: 3.69 Å EMDB-23454: Human p97 in complex with Npl4/Ufd1 and polyubiquitinated Ub-Eos in the presence of ATP and sub-stoichiometric NMS-873 (Class 2) 手法: EM (単粒子) / 解像度: 6.0 Å EMDB-23455: Human p97 in complex with Npl4/Ufd1 and polyubiquitinated Ub-Eos in the presence of ATP and sub-stoichiometric NMS-873 (Class 3) 手法: EM (単粒子) / 解像度: 3.58 Å EMDB-23456: Human p97 in complex with Npl4/Ufd1 and polyubiquitinated Ub-Eos in the presence of ATP and sub-stoichiometric NMS-873 (Class 4) 手法: EM (単粒子) / 解像度: 4.25 Å EMDB-23457: Human p97 in complex with Npl4/Ufd1 and polyubiquitinated Ub-Eos in the presence of ATP and sub-stoichiometric NMS-873 (Class 5) 手法: EM (単粒子) / 解像度: 3.47 Å EMDB-23458: Human p97 in complex with Npl4/Ufd1 and polyubiquitinated Ub-Eos in the presence of ATP and sub-stoichiometric NMS-873 (Class 6) 手法: EM (単粒子) / 解像度: 3.65 Å
化合物	ChemComp-ATP: ADENOSINE-5'-TRIPHOSPHATE / ATP / ATP, エネルギー貯蔵分子YM ChemComp-Y6Y: 3-[3-cyclopentylsulfanyl-5-[[3-methyl-4-(4-methylsulfonylphenyl)phenoxy]methyl]-1,2,4-triazol-4-yl]pyridine / 3-[[2-メチル-4′-(メチルスルホニル)-4-ビフェニリルオキシ]メチル]-4-(3-ピリジル)-5-(シクロペ(以下略) ChemComp-MG: Unknown entry / マグネシウムジカチオン ChemComp-ADP: ADENOSINE-5'-DIPHOSPHATE / ADP / ADP, エネルギー貯蔵分子YM
由来	homo sapiens (ヒト) mus musculus (ハツカネズミ)
キーワード	TRANSLOCASE / p97 / NMS-873 / single-particle cryo-EM / translocation / allosteric inhibition