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	USP14-regulated allostery of the human proteasome by time-resolved cryo-EM.
ジャーナル・号・ページ	Nature, Vol. 605, Issue 7910, Page 567-574, Year 2022
掲載日	2022年4月27日
著者	Shuwen Zhang / Shitao Zou / Deyao Yin / Lihong Zhao / Daniel Finley / Zhaolong Wu / Youdong Mao /
PubMed 要旨	Proteasomal degradation of ubiquitylated proteins is tightly regulated at multiple levels. A primary regulatory checkpoint is the removal of ubiquitin chains from substrates by the deubiquitylating ...Proteasomal degradation of ubiquitylated proteins is tightly regulated at multiple levels. A primary regulatory checkpoint is the removal of ubiquitin chains from substrates by the deubiquitylating enzyme ubiquitin-specific protease 14 (USP14), which reversibly binds the proteasome and confers the ability to edit and reject substrates. How USP14 is activated and regulates proteasome function remain unknown. Here we present high-resolution cryo-electron microscopy structures of human USP14 in complex with the 26S proteasome in 13 distinct conformational states captured during degradation of polyubiquitylated proteins. Time-resolved cryo-electron microscopy analysis of the conformational continuum revealed two parallel pathways of proteasome state transitions induced by USP14, and captured transient conversion of substrate-engaged intermediates into substrate-inhibited intermediates. On the substrate-engaged pathway, ubiquitin-dependent activation of USP14 allosterically reprograms the conformational landscape of the AAA-ATPase motor and stimulates opening of the core particle gate, enabling observation of a near-complete cycle of asymmetric ATP hydrolysis around the ATPase ring during processive substrate unfolding. Dynamic USP14-ATPase interactions decouple the ATPase activity from RPN11-catalysed deubiquitylation and kinetically introduce three regulatory checkpoints on the proteasome, at the steps of ubiquitin recognition, substrate translocation initiation and ubiquitin chain recycling. These findings provide insights into the complete functional cycle of the USP14-regulated proteasome and establish mechanistic foundations for the discovery of USP14-targeted therapies.
リンク	Nature / PubMed:35477760 / PubMed Central
手法	EM (単粒子)
解像度	3.0 - 3.6 Å
構造データ	32272 7w37 EMDB-32272, PDB-7w37: Structure of USP14-bound human 26S proteasome in state EA1_UBL 手法: EM (単粒子) / 解像度: 3.0 Å 32273 7w38 EMDB-32273, PDB-7w38: Structure of USP14-bound human 26S proteasome in state EA2.0_UBL 手法: EM (単粒子) / 解像度: 3.1 Å 32274 7w39 EMDB-32274, PDB-7w39: Structure of USP14-bound human 26S proteasome in state EA2.1_UBL 手法: EM (単粒子) / 解像度: 3.2 Å 32275 7w3a EMDB-32275, PDB-7w3a: Structure of USP14-bound human 26S proteasome in substrate-engaged state ED4_USP14 手法: EM (単粒子) / 解像度: 3.5 Å 32276 7w3b EMDB-32276, PDB-7w3b: Structure of USP14-bound human 26S proteasome in substrate-engaged state ED5_USP14 手法: EM (単粒子) / 解像度: 3.6 Å 32277 7w3c EMDB-32277, PDB-7w3c: Structure of USP14-bound human 26S proteasome in substrate-engaged state ED0_USP14 手法: EM (単粒子) / 解像度: 3.4 Å 32278 7w3f EMDB-32278, PDB-7w3f: Structure of USP14-bound human 26S proteasome in substrate-engaged state ED1_USP14 手法: EM (単粒子) / 解像度: 3.3 Å 32279 7w3g EMDB-32279, PDB-7w3g: Structure of USP14-bound human 26S proteasome in substrate-engaged state ED2.0_USP14 手法: EM (単粒子) / 解像度: 3.2 Å 32280 7w3h EMDB-32280, PDB-7w3h: Structure of USP14-bound human 26S proteasome in substrate-engaged state ED2.1_USP14 手法: EM (単粒子) / 解像度: 3.2 Å 32281 7w3i EMDB-32281, PDB-7w3i: Structure of USP14-bound human 26S proteasome in substrate-inhibited state SB_USP14 手法: EM (単粒子) / 解像度: 3.5 Å 32282 7w3j EMDB-32282, PDB-7w3j: Structure of USP14-bound human 26S proteasome in substrate-inhibited state SC_USP14 手法: EM (単粒子) / 解像度: 3.5 Å 32283 7w3k EMDB-32283, PDB-7w3k: Structure of USP14-bound human 26S proteasome in substrate-inhibited state SD4_USP14 手法: EM (単粒子) / 解像度: 3.6 Å 32284 7w3m EMDB-32284, PDB-7w3m: Structure of USP14-bound human 26S proteasome in substrate-inhibited state SD5_USP14 手法: EM (単粒子) / 解像度: 3.5 Å EMDB-32285: Structure of USP14-bound human 26S proteasome in state EA1_UBL with the local RPN1 density improved 手法: EM (単粒子) / 解像度: 3.3 Å EMDB-32286: Structure of USP14-bound human 26S proteasome in state EA2.0_UBL with the local RPN1 density improved 手法: EM (単粒子) / 解像度: 3.3 Å EMDB-32287: Structure of USP14-bound human 26S proteasome in state EA2.1_UBL with the local RPN1 density improved 手法: EM (単粒子) / 解像度: 3.3 Å EMDB-32288: Structure of USP14-bound human 26S proteasome in substrate-engaged state ED4_USP14 with the USP14 density improved 手法: EM (単粒子) / 解像度: 3.5 Å EMDB-32289: Structure of USP14-bound human 26S proteasome in substrate-engaged state ED0_USP14 with the RPN1 density improved 手法: EM (単粒子) / 解像度: 3.5 Å EMDB-32290: Structure of USP14-bound human 26S proteasome in substrate-engaged state ED2.0_USP14 with the RPN1 density improved 手法: EM (単粒子) / 解像度: 3.4 Å EMDB-32291: Structure of USP14-bound human 26S proteasome in substrate-engaged state ED2.1_USP14 with the USP14 density improved 手法: EM (単粒子) / 解像度: 3.3 Å EMDB-32292: Structure of USP14-bound human 26S proteasome in substrate-inhibited state SC_USP14 with the USP14 density improved 手法: EM (単粒子) / 解像度: 3.6 Å
化合物	ChemComp-ATP: ADENOSINE-5'-TRIPHOSPHATE / ATP / ATP, エネルギー貯蔵分子YM / アデノシン三リン酸 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 / アデノシン二リン酸 ChemComp-ZN: Unknown entry
由来	homo sapiens (ヒト) saccharomyces cerevisiae (パン酵母)
キーワード	HYDROLASE (加水分解酵素) / Proteasome (プロテアソーム) / AAA-ATPase / Deubiquitinase (脱ユビキチン化酵素) / USP14