登録情報 データベース : EMDB / ID : EMD-14597 ダウンロードとリンクタイトル CAND1 delhairpin-SCF-SKP2 CAND1 partly engaged SCF partly rocked マップデータdeepEMhancer 詳細 試料複合体 : CAND1 delhairpin-SCF-SKP2 CAND1 partly engaged SCF partly rocked複合体 : Cullin-associated NEDD8-dissociated protein 1and S-phase kinase-associated protein 1 and 2タンパク質・ペプチド : Cullin-associated NEDD8-dissociated protein 1タンパク質・ペプチド : S-phase kinase-associated protein 1タンパク質・ペプチド : S-phase kinase-associated protein 2複合体 : Cullin-1 and E3 ubiquitin-protein ligase RBX1タンパク質・ペプチド : Cullin-1タンパク質・ペプチド : E3 ubiquitin-protein ligase RBX1リガンド : ZINC ION 詳細機能・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
SCF complex assembly / positive regulation of protein polyubiquitination / Parkin-FBXW7-Cul1 ubiquitin ligase complex / F-box domain binding / Aberrant regulation of mitotic exit in cancer due to RB1 defects / PcG protein complex / negative regulation of catalytic activity / cullin-RING ubiquitin ligase complex / Cul7-RING ubiquitin ligase complex / positive regulation of ubiquitin protein ligase activity ... SCF complex assembly / positive regulation of protein polyubiquitination / Parkin-FBXW7-Cul1 ubiquitin ligase complex / F-box domain binding / Aberrant regulation of mitotic exit in cancer due to RB1 defects / PcG protein complex / negative regulation of catalytic activity / cullin-RING ubiquitin ligase complex / Cul7-RING ubiquitin ligase complex / positive regulation of ubiquitin protein ligase activity / Loss of Function of FBXW7 in Cancer and NOTCH1 Signaling / maintenance of protein location in nucleus / positive regulation of protein autoubiquitination / protein neddylation / NEDD8 ligase activity / Cul5-RING ubiquitin ligase complex / positive regulation of intracellular estrogen receptor signaling pathway / ubiquitin-ubiquitin ligase activity / Cul4A-RING E3 ubiquitin ligase complex / SCF ubiquitin ligase complex / Cul2-RING ubiquitin ligase complex / Cul4B-RING E3 ubiquitin ligase complex / ubiquitin ligase complex scaffold activity / SCF-dependent proteasomal ubiquitin-dependent protein catabolic process / Cul3-RING ubiquitin ligase complex / Prolactin receptor signaling / protein monoubiquitination / cullin family protein binding / protein K63-linked ubiquitination / ubiquitin-like ligase-substrate adaptor activity / positive regulation of double-strand break repair via homologous recombination / positive regulation of RNA polymerase II transcription preinitiation complex assembly / protein K48-linked ubiquitination / Nuclear events stimulated by ALK signaling in cancer / ubiquitin ligase complex / TBP-class protein binding / Regulation of BACH1 activity / intrinsic apoptotic signaling pathway / MAP3K8 (TPL2)-dependent MAPK1/3 activation / SCF-beta-TrCP mediated degradation of Emi1 / NIK-->noncanonical NF-kB signaling / molecular function activator activity / Vpu mediated degradation of CD4 / Dectin-1 mediated noncanonical NF-kB signaling / Degradation of GLI1 by the proteasome / Activation of NF-kappaB in B cells / animal organ morphogenesis / Negative regulation of NOTCH4 signaling / Iron uptake and transport / GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2 / Degradation of GLI2 by the proteasome / GLI3 is processed to GLI3R by the proteasome / FBXL7 down-regulates AURKA during mitotic entry and in early mitosis / APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1 / Degradation of beta-catenin by the destruction complex / NOTCH1 Intracellular Domain Regulates Transcription / CLEC7A (Dectin-1) signaling / beta-catenin binding / SCF(Skp2)-mediated degradation of p27/p21 / Constitutive Signaling by NOTCH1 PEST Domain Mutants / Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants / FCERI mediated NF-kB activation / Interleukin-1 signaling / Orc1 removal from chromatin / G1/S transition of mitotic cell cycle / protein polyubiquitination / G2/M transition of mitotic cell cycle / Regulation of RUNX2 expression and activity / Cyclin D associated events in G1 / Regulation of PLK1 Activity at G2/M Transition / ubiquitin protein ligase activity / Circadian Clock / Antigen processing: Ubiquitination & Proteasome degradation / positive regulation of proteasomal ubiquitin-dependent protein catabolic process / Downstream TCR signaling / protein-macromolecule adaptor activity / Neddylation / mitotic cell cycle / ubiquitin-dependent protein catabolic process / regulation of apoptotic process / proteasome-mediated ubiquitin-dependent protein catabolic process / secretory granule lumen / positive regulation of canonical NF-kappaB signal transduction / defense response to virus / RNA polymerase II-specific DNA-binding transcription factor binding / ficolin-1-rich granule lumen / cell population proliferation / cell differentiation / Ub-specific processing proteases / regulation of cell cycle / protein ubiquitination / chromatin remodeling / protein domain specific binding / innate immune response / centrosome / ubiquitin protein ligase binding / Neutrophil degranulation / nucleolus / Golgi apparatus / zinc ion binding 類似検索 - 分子機能 TATA-binding protein interacting (TIP20) / Cullin-associated NEDD8-dissociated protein 1/2 / TATA-binding protein interacting (TIP20) / Leucine-rich repeat, cysteine-containing subtype / Leucine-rich repeat - CC (cysteine-containing) subfamily / A Receptor for Ubiquitination Targets / F-box domain profile. / F-box-like domain superfamily / F-box-like / SKP1 component, dimerisation ... TATA-binding protein interacting (TIP20) / Cullin-associated NEDD8-dissociated protein 1/2 / TATA-binding protein interacting (TIP20) / Leucine-rich repeat, cysteine-containing subtype / Leucine-rich repeat - CC (cysteine-containing) subfamily / A Receptor for Ubiquitination Targets / F-box domain profile. / F-box-like domain superfamily / F-box-like / SKP1 component, dimerisation / S-phase kinase-associated protein 1 / SKP1-like, dimerisation domain superfamily / Skp1 family, dimerisation domain / HEAT-like repeat / F-box domain / Zinc finger, RING-H2-type / RING-H2 zinc finger domain / Cullin protein neddylation domain / Cullin, conserved site / Cullin family signature. / Cullin / Cullin repeat-like-containing domain superfamily / Cullin protein, neddylation domain / Cullin protein neddylation domain / Cullin / Cullin, N-terminal / Cullin homology domain / Cullin homology domain superfamily / Cullin family / Cullin family profile. / S-phase kinase-associated protein 1-like / SKP1 component, POZ domain / Skp1 family, tetramerisation domain / Found in Skp1 protein family / SKP1/BTB/POZ domain superfamily / Leucine-rich repeat domain superfamily / Zinc finger RING-type profile. / Zinc finger, RING-type / Armadillo-like helical / Armadillo-type fold / Zinc finger, RING/FYVE/PHD-type / Winged helix DNA-binding domain superfamily / Winged helix-like DNA-binding domain superfamily 類似検索 - ドメイン・相同性 E3 ubiquitin-protein ligase RBX1 / S-phase kinase-associated protein 1 / S-phase kinase-associated protein 2 / Cullin-1 / Cullin-associated NEDD8-dissociated protein 1 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 : 3.1 Å 詳細 データ登録者Baek K / Schulman BA 資金援助 ドイツ, European Union, 2件 詳細 詳細を隠すOrganization Grant number 国 Max Planck Society ドイツ European Research Council (ERC) 789016 European Union
引用ジャーナル : Cell / 年 : 2023タイトル : Systemwide disassembly and assembly of SCF ubiquitin ligase complexes.著者 : Kheewoong Baek / Daniel C Scott / Lukas T Henneberg / Moeko T King / Matthias Mann / Brenda A Schulman / 要旨 : Cells respond to environmental cues by remodeling their inventories of multiprotein complexes. Cellular repertoires of SCF (SKP1-CUL1-F box protein) ubiquitin ligase complexes, which mediate much ... Cells respond to environmental cues by remodeling their inventories of multiprotein complexes. Cellular repertoires of SCF (SKP1-CUL1-F box protein) ubiquitin ligase complexes, which mediate much protein degradation, require CAND1 to distribute the limiting CUL1 subunit across the family of ∼70 different F box proteins. Yet, how a single factor coordinately assembles numerous distinct multiprotein complexes remains unknown. We obtained cryo-EM structures of CAND1-bound SCF complexes in multiple states and correlated mutational effects on structures, biochemistry, and cellular assays. The data suggest that CAND1 clasps idling catalytic domains of an inactive SCF, rolls around, and allosterically rocks and destabilizes the SCF. New SCF production proceeds in reverse, through SKP1-F box allosterically destabilizing CAND1. The CAND1-SCF conformational ensemble recycles CUL1 from inactive complexes, fueling mixing and matching of SCF parts for E3 activation in response to substrate availability. Our data reveal biogenesis of a predominant family of E3 ligases, and the molecular basis for systemwide multiprotein complex assembly. 履歴 登録 2022年3月24日 - ヘッダ(付随情報) 公開 2023年4月19日 - マップ公開 2023年4月19日 - 更新 2023年5月10日 - 現状 2023年5月10日 処理サイト : PDBe / 状態 : 公開
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