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基本情報
登録情報 | データベース: PDB / ID: 7okq | ||||||
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タイトル | Cryo-EM Structure of the DDB1-DCAF1-CUL4A-RBX1 Complex | ||||||
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![]() | LIGASE / ubiquitin / E3 / protein degradation | ||||||
機能・相同性 | ![]() histone H2AT120 kinase activity / cell competition in a multicellular organism / negative regulation of granulocyte differentiation / cullin-RING-type E3 NEDD8 transferase / cellular response to chemical stress / NEDD8 transferase activity / cullin-RING ubiquitin ligase complex / regulation of DNA damage checkpoint / V(D)J recombination / positive regulation by virus of viral protein levels in host cell ...histone H2AT120 kinase activity / cell competition in a multicellular organism / negative regulation of granulocyte differentiation / cullin-RING-type E3 NEDD8 transferase / cellular response to chemical stress / NEDD8 transferase activity / cullin-RING ubiquitin ligase complex / regulation of DNA damage checkpoint / V(D)J recombination / positive regulation by virus of viral protein levels in host cell / Cul7-RING ubiquitin ligase complex / ubiquitin-dependent protein catabolic process via the C-end degron rule pathway / regulation of nucleotide-excision repair / epigenetic programming in the zygotic pronuclei / Loss of Function of FBXW7 in Cancer and NOTCH1 Signaling / spindle assembly involved in female meiosis / positive regulation of protein autoubiquitination / Cul4-RING E3 ubiquitin ligase complex / UV-damage excision repair / protein neddylation / NEDD8 ligase activity / Cul5-RING ubiquitin ligase complex / biological process involved in interaction with symbiont / negative regulation of response to oxidative stress / regulation of mitotic cell cycle phase transition / ubiquitin-ubiquitin ligase activity / Cul4A-RING E3 ubiquitin ligase complex / SCF ubiquitin ligase complex / Cul2-RING ubiquitin ligase complex / WD40-repeat domain binding / ubiquitin ligase complex scaffold activity / Cul4B-RING E3 ubiquitin ligase complex / negative regulation of type I interferon production / SCF-dependent proteasomal ubiquitin-dependent protein catabolic process / Cul3-RING ubiquitin ligase complex / Prolactin receptor signaling / negative regulation of reproductive process / negative regulation of developmental process / protein monoubiquitination / cullin family protein binding / somatic stem cell population maintenance / hemopoiesis / viral release from host cell / ubiquitin-like ligase-substrate adaptor activity / ectopic germ cell programmed cell death / proteasomal protein catabolic process / positive regulation of G1/S transition of mitotic cell cycle / protein K48-linked ubiquitination / positive regulation of viral genome replication / Nuclear events stimulated by ALK signaling in cancer / positive regulation of gluconeogenesis / positive regulation of TORC1 signaling / T cell activation / regulation of cellular response to insulin stimulus / Regulation of BACH1 activity / intrinsic apoptotic signaling pathway / B cell differentiation / post-translational protein modification / Degradation of DVL / nuclear estrogen receptor binding / nucleotide-excision repair / Recognition of DNA damage by PCNA-containing replication complex / Degradation of GLI1 by the proteasome / Negative regulation of NOTCH4 signaling / cellular response to amino acid stimulus / GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2 / Vif-mediated degradation of APOBEC3G / Hedgehog 'on' state / 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 / DNA Damage Recognition in GG-NER / RING-type E3 ubiquitin transferase / negative regulation of canonical Wnt signaling pathway / Degradation of beta-catenin by the destruction complex / Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha / regulation of circadian rhythm / Transcription-Coupled Nucleotide Excision Repair (TC-NER) / Formation of TC-NER Pre-Incision Complex / Dual Incision in GG-NER / Evasion by RSV of host interferon responses / NOTCH1 Intracellular Domain Regulates Transcription / Wnt signaling pathway / fibrillar center / Constitutive Signaling by NOTCH1 PEST Domain Mutants / Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants / Regulation of expression of SLITs and ROBOs / Formation of Incision Complex in GG-NER / Dual incision in TC-NER / Interleukin-1 signaling / Orc1 removal from chromatin / Gap-filling DNA repair synthesis and ligation in TC-NER / Regulation of RAS by GAPs / protein polyubiquitination / positive regulation of protein catabolic process / G1/S transition of mitotic cell cycle / Regulation of RUNX2 expression and activity / cellular response to UV / MAPK cascade / ubiquitin protein ligase activity 類似検索 - 分子機能 | ||||||
生物種 | ![]() | ||||||
手法 | 電子顕微鏡法 / 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 8.4 Å | ||||||
![]() | Mohamed, W.I. / Schenk, A.D. / Kempf, G. / Cavadini, S. / Thoma, N.H. | ||||||
![]() | ![]() タイトル: The CRL4 cullin-RING ubiquitin ligase is activated following a switch in oligomerization state. 著者: Weaam I Mohamed / Andreas D Schenk / Georg Kempf / Simone Cavadini / Anja Basters / Alessandro Potenza / Wassim Abdul Rahman / Julius Rabl / Kurt Reichermeier / Nicolas H Thomä / ![]() ![]() 要旨: The cullin-4-based RING-type (CRL4) family of E3 ubiquitin ligases functions together with dedicated substrate receptors. Out of the ˜29 CRL4 substrate receptors reported, the DDB1- and CUL4- ...The cullin-4-based RING-type (CRL4) family of E3 ubiquitin ligases functions together with dedicated substrate receptors. Out of the ˜29 CRL4 substrate receptors reported, the DDB1- and CUL4-associated factor 1 (DCAF1) is essential for cellular survival and growth, and its deregulation has been implicated in tumorigenesis. We carried out biochemical and structural studies to examine the structure and mechanism of the CRL4 ligase. In the 8.4 Å cryo-EM map of CRL4 , four CUL4-RBX1-DDB1-DCAF1 protomers are organized into two dimeric sub-assemblies. In this arrangement, the WD40 domain of DCAF1 mediates binding with the cullin C-terminal domain (CTD) and the RBX1 subunit of a neighboring CRL4 protomer. This renders RBX1, the catalytic subunit of the ligase, inaccessible to the E2 ubiquitin-conjugating enzymes. Upon CRL4 activation by neddylation, the interaction between the cullin CTD and the neighboring DCAF1 protomer is broken, and the complex assumes an active dimeric conformation. Accordingly, a tetramerization-deficient CRL4 mutant has higher ubiquitin ligase activity compared to the wild-type. This study identifies a novel mechanism by which unneddylated and substrate-free CUL4 ligases can be maintained in an inactive state. | ||||||
履歴 |
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構造の表示
ムービー |
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構造ビューア | 分子: ![]() ![]() |
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PDBx/mmCIF形式 | ![]() | 1.3 MB | 表示 | ![]() |
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PDB形式 | ![]() | 839.3 KB | 表示 | ![]() |
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その他 | ![]() |
-検証レポート
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
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-関連構造データ
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リンク
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集合体
登録構造単位 | ![]()
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1 | ![]()
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要素
#1: タンパク質 | 分子量: 129394.898 Da / 分子数: 4 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() #2: タンパク質 | 分子量: 171279.094 Da / 分子数: 4 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() 参照: UniProt: Q9Y4B6, non-specific serine/threonine protein kinase #3: タンパク質 | 分子量: 86702.836 Da / 分子数: 4 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() #4: タンパク質 | 分子量: 13497.240 Da / 分子数: 4 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() 参照: UniProt: P62877, RING-type E3 ubiquitin transferase, cullin-RING-type E3 NEDD8 transferase |
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-実験情報
-実験
実験 | 手法: 電子顕微鏡法 |
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EM実験 | 試料の集合状態: PARTICLE / 3次元再構成法: 単粒子再構成法 |
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試料調製
構成要素 | 名称: CRL4(DCAF1) / タイプ: COMPLEX / Entity ID: all / 由来: RECOMBINANT |
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由来(天然) | 生物種: ![]() |
由来(組換発現) | 生物種: ![]() |
緩衝液 | pH: 7.4 |
試料 | 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES |
急速凍結 | 凍結剤: ETHANE |
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電子顕微鏡撮影
実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |
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顕微鏡 | モデル: FEI TITAN KRIOS |
電子銃 | 電子線源: ![]() |
電子レンズ | モード: BRIGHT FIELD |
撮影 | 電子線照射量: 45 e/Å2 フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) |
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解析
EMソフトウェア |
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CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | |||||||||||||||||||||
3次元再構成 | 解像度: 8.4 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 14000 / 対称性のタイプ: POINT | |||||||||||||||||||||
原子モデル構築 | B value: 596 / プロトコル: FLEXIBLE FIT / 空間: REAL / Target criteria: Real-space cross-correlation | |||||||||||||||||||||
原子モデル構築 |
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