登録情報 データベース : EMDB / ID : EMD-53258 ダウンロードとリンクタイトル 9-subunit COP9 signalosome complex マップデータ 詳細 試料複合体 : COP9 signalosomeリガンド : x 2種 詳細 キーワード COP9 signalosome / HYDROLASE機能・相同性 機能・相同性情報分子機能 ドメイン・相同性 構成要素
negative regulation of protein localization to nucleolus / COP9 signalosome assembly / trophectodermal cell proliferation / macrophage migration inhibitory factor binding / regulation of IRE1-mediated unfolded protein response / exosomal secretion / GTPase inhibitor activity / deNEDDylase activity / protein deneddylation / regulation of protein neddylation ... negative regulation of protein localization to nucleolus / COP9 signalosome assembly / trophectodermal cell proliferation / macrophage migration inhibitory factor binding / regulation of IRE1-mediated unfolded protein response / exosomal secretion / GTPase inhibitor activity / deNEDDylase activity / protein deneddylation / regulation of protein neddylation / activation of NF-kappaB-inducing kinase activity / eukaryotic translation initiation factor 3 complex / COP9 signalosome / negative regulation of protein neddylation / protein neddylation / 加水分解酵素; プロテアーゼ; ペプチド結合加水分解酵素 / regulation of JNK cascade / RHOBTB1 GTPase cycle / metal-dependent deubiquitinase activity / regulation of DNA damage response, signal transduction by p53 class mediator / inner cell mass cell proliferation / response to light stimulus / skeletal muscle cell differentiation / : / JNK cascade / translation initiation factor activity / post-translational protein modification / DNA Damage Recognition in GG-NER / Formation of TC-NER Pre-Incision Complex / metallopeptidase activity / neuron differentiation / synaptic vesicle / cellular response to UV / cell junction / transcription corepressor activity / Cargo recognition for clathrin-mediated endocytosis / Neddylation / ubiquitin-dependent protein catabolic process / in utero embryonic development / transcription by RNA polymerase II / transcription coactivator activity / protein phosphorylation / regulation of cell cycle / nuclear speck / translation / negative regulation of cell population proliferation / positive regulation of cell population proliferation / negative regulation of apoptotic process / chromatin / perinuclear region of cytoplasm / enzyme binding / negative regulation of transcription by RNA polymerase II / signal transduction / positive regulation of transcription by RNA polymerase II / proteolysis / extracellular exosome / nucleoplasm / metal ion binding / nucleus / cytosol / cytoplasm 類似検索 - 分子機能 COP9 signalosome complex, subunit 9, metazoa / Myeloma-overexpressed-like / COP9 signalosome complex subunit 7, helix I / : / COP9 signalosome complex subunit 7a helix I domain / COP9 signalosome complex subunit 3-like, C-terminal helix / CSN7 helical bundle subdomain / COP9 signalosome, subunit CSN8 / COP9 signalosome complex subunit 4, helix turn helix domain / : ... COP9 signalosome complex, subunit 9, metazoa / Myeloma-overexpressed-like / COP9 signalosome complex subunit 7, helix I / : / COP9 signalosome complex subunit 7a helix I domain / COP9 signalosome complex subunit 3-like, C-terminal helix / CSN7 helical bundle subdomain / COP9 signalosome, subunit CSN8 / COP9 signalosome complex subunit 4, helix turn helix domain / : / CSN4/RPN5/eIF3a helix turn helix domain / COP9 signalosome complex subunit 3, N-terminal helical repeats / COP9 signalosome subunit 6 / : / COP9 signalosome complex subunit 1, C-terminal helix / Cop9 signalosome subunit 5 C-terminal domain / Cop9 signalosome subunit 5 C-terminal domain / Eukaryotic translation initiation factor 3 subunit M eIF3m/COP9 signalosome complex subunit 7 COPS7 / : / : / : / PSMD12/CSN4, N-terminal / 26S proteasome regulatory subunit Rpn7/COP9 signalosome complex subunit 1 / 26S proteasome regulatory subunit Rpn7, N-terminal / 26S proteasome subunit RPN7 / 26S Proteasome non-ATPase regulatory subunit 12/COP9 signalosome complex subunit 4 / PCI/PINT associated module / CSN8/PSMD8/EIF3K / CSN8/PSMD8/EIF3K family / Rpn11/EIF3F, C-terminal / Maintenance of mitochondrial structure and function / : / motif in proteasome subunits, Int-6, Nip-1 and TRIP-15 / PCI domain / Proteasome component (PCI) domain / PCI domain profile. / JAB1/Mov34/MPN/PAD-1 ubiquitin protease / JAB/MPN domain / JAB1/MPN/MOV34 metalloenzyme domain / MPN domain / MPN domain profile. / Tetratricopeptide-like helical domain superfamily / Winged helix DNA-binding domain superfamily / Winged helix-like DNA-binding domain superfamily 類似検索 - ドメイン・相同性 COP9 signalosome complex subunit 2 / COP9 signalosome complex subunit 1 / COP9 signalosome complex subunit 6 / COP9 signalosome complex subunit 9 / COP9 signalosome complex subunit 5 / COP9 signalosome complex subunit 8 / COP9 signalosome complex subunit 4 / COP9 signalosome complex subunit 7b / COP9 signalosome complex subunit 3 類似検索 - 構成要素生物種 Homo sapiens (ヒト)手法 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度 : 3.0 Å 詳細 データ登録者Ding S / Clapperton JA / Maeots ME / Enchev RI 資金援助 英国, 1件 詳細 詳細を隠すOrganization Grant number 国 The Francis Crick Institute CC2059 英国
引用ジャーナル : Nat Commun / 年 : 2026タイトル : Structural basis of CSN-mediated SCF deneddylation.著者 : Shan Ding / Julie A Clapperton / Märt-Erik Mäeots / Simone Kunzelmann / Mohammed Shaaban / Radoslav I Enchev / 要旨 : Cullin-RING ligases (CRLs) are the largest family of E3 ligases, with ubiquitination activity dynamically regulated by neddylation and deneddylation by the COP9 signalosome (CSN). CSN-mediated ... Cullin-RING ligases (CRLs) are the largest family of E3 ligases, with ubiquitination activity dynamically regulated by neddylation and deneddylation by the COP9 signalosome (CSN). CSN-mediated deneddylation not only deactivates CRLs but also enables substrate receptor exchange. Although CSN is a promising drug target, the structural basis underlying its catalytic mechanism remains unclear. Here, we use cryo-electron microscopy (cryo-EM) to uncover distinct functional states of CSN-CRL (SCF) complexes, capturing key intermediates of the deneddylation cycle. We visualise an autoinhibited docking state and a catalytic intermediate in which CSN5 Ins-1 loop, RBX1 RING and neddylated Cullin WHB domains are repositioned for isopeptide cleavage. We further resolve four dissociation intermediates that define the stepwise release of CSN from its product, with RBX1 RING stabilising key interactions. Additionally, our structures locate CSNAP within a CSN3-CSN8 groove. Together, our study provides a mechanistic model for CSN function and informs the rational design of CSN-targeted therapeutics. 履歴 登録 2025年3月25日 - ヘッダ(付随情報) 公開 2026年2月4日 - マップ公開 2026年2月4日 - 更新 2026年2月4日 - 現状 2026年2月4日 処理サイト : PDBe / 状態 : 公開
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