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	Structural dynamics of the midnolin-proteasome during ubiquitin-independent substrate turnover.
ジャーナル・号・ページ	Nat Commun, Vol. 17, Issue 1, Year 2026
掲載日	2026年3月27日
著者	Chuanda Zhu / Lu Qin / Zonglin Dai / Peng Zuo / Ao Yang / Lijun Zhong / Zhiqiang Lin / Ling Liang /
PubMed 要旨	The 26S proteasome typically degrades proteins marked by ubiquitin chains. However, a distinct, ubiquitin-independent degradation pathway for nuclear proteins exists, mediated by the adaptor protein ...The 26S proteasome typically degrades proteins marked by ubiquitin chains. However, a distinct, ubiquitin-independent degradation pathway for nuclear proteins exists, mediated by the adaptor protein midnolin, yet its molecular mechanism remains poorly understood. Here, we present nine cryo-electron microscopy structures of the human 26S proteasome in complex with midnolin, which collectively delineate a near-complete catalytic cycle. Our structures reveal that midnolin binds to the proteasome via the RPN1 subunit by its C-terminal helix. Unexpectedly, its ubiquitin-like domain interacts with the RPN11 deubiquitinase in a non-catalytic role. This interaction positions the adjacent Catch domain, which is responsible for substrate binding, directly above the proteasomal entrance, potentially facilitating substrate entry into the proteasome. Furthermore, we observe four consecutive spiral staircase conformations of the AAA+ ATPase hexamer during substrate translocation. These findings provide insights into the mechanisms underlying ubiquitin-independent nuclear protein degradation and may help develop strategies for targeting nuclear proteins via direct proteasomal degradation.
リンク	Nat Commun / PubMed:41896529 / PubMed Central
手法	EM (単粒子)
解像度	2.75 - 4.23 Å
構造データ	EMDB-63725: Focused refinement of 19S in the substrate-engaged human 26S proteasome bound to midnolin with RPT1 at top of spiral staircase 手法: EM (単粒子) / 解像度: 3.34 Å EMDB-63726: Consensus map of substrate-engaged human 26S proteasome bound to midnolin with RPT1 at top of spiral staircase 手法: EM (単粒子) / 解像度: 2.75 Å EMDB-63727: Consensus map of substrate-engaged human 26S proteasome bound to midnolin with RPT5 at top of spiral staircase 手法: EM (単粒子) / 解像度: 2.93 Å EMDB-63728: Focused refinement of 19S in the substrate-engaged human 26S proteasome bound to midnolin with RPT5 at top of spiral staircase 手法: EM (単粒子) / 解像度: 3.44 Å EMDB-63751: Consensus map of substrate-engaged human 26S proteasome bound to midnolin with RPT2 at top of spiral staircase 手法: EM (単粒子) / 解像度: 2.91 Å EMDB-63752: Focused refinement of 19S in the substrate-engaged human 26S proteasome bound to midnolin with RPT2 at top of spiral staircase 手法: EM (単粒子) / 解像度: 3.5 Å 63775 9mbo EMDB-63775, PDB-9mbo: Focused refinement of RPN1 and the C-terminal helix of midnolin in the substrate-engaged human 26S proteasome 手法: EM (単粒子) / 解像度: 2.83 Å 63776 9mbp EMDB-63776, PDB-9mbp: Substrate-engaged human 26S proteasome bound to midnolin with RPT1 at top of spiral staircase 手法: EM (単粒子) / 解像度: 2.75 Å 63777 9mbq EMDB-63777, PDB-9mbq: Substrate-engaged human 26S proteasome bound to midnolin with RPT5 at top of spiral staircase 手法: EM (単粒子) / 解像度: 3.08 Å 63817 9u3l EMDB-63817, PDB-9u3l: Substrate-engaged human 26S proteasome bound to midnolin with RPT2 at top of spiral staircase 手法: EM (単粒子) / 解像度: 2.91 Å 63850 9u4m EMDB-63850, PDB-9u4m: Focused refinement of 19S in the substrate-engaged human 26S proteasome bound to midnolin with RPT6 at top of spiral staircase 手法: EM (単粒子) / 解像度: 4.14 Å 63943 9u7r EMDB-63943, PDB-9u7r: Substrate-free human 26S proteasome purified by midnolin, 20S proteasome, RPTs and RPN11 part 手法: EM (単粒子) / 解像度: 3.17 Å 65595 9w39 EMDB-65595, PDB-9w39: Structure of human 26S proteasome complexed with midnolin, 19S proteasome with Ubl bound 手法: EM (単粒子) / 解像度: 3.65 Å 65839 9wbg EMDB-65839, PDB-9wbg: Structure of human 26S proteasome complexed with midnolin, 19S proteasome with Ubl and Catch domain resolved 手法: EM (単粒子) / 解像度: 4.23 Å 68472 22mm EMDB-68472, PDB-22mm: Structure of human 26S proteasome complexed with midnolin(1-111+337-468) 手法: EM (単粒子) / 解像度: 3.42 Å
化合物	ChemComp-ZN: Unknown entry ChemComp-ATP: ADENOSINE-5'-TRIPHOSPHATE / ATP, エネルギー貯蔵分子YM ChemComp-MG: Unknown entry ChemComp-ADP: ADENOSINE-5'-DIPHOSPHATE / ADP, エネルギー貯蔵分子YM ChemComp-LDZ: N-[(benzyloxy)carbonyl]-L-leucyl-N-[(2S)-4-methyl-1-oxopentan-2-yl]-L-leucinamide / 阻害剤*YM
由来	homo sapiens (ヒト) purpureocillium lilacinum (菌類) pseudotamlana agarivorans (バクテリア) synthetic construct (人工物) escherichia coli str. k-12 substr. mg1655 (大腸菌) escherichia coli k-12 (大腸菌)
キーワード	HYDROLASE / 26S proteasome / midnolin / Complex / proteasome