+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 8cdk | |||||||||
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タイトル | CAND1 b-hairpin++-SCF-SKP2 CAND1 partly engaged SCF partly rocked | |||||||||
要素 |
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キーワード | LIGASE / cullin-RING E3 ubiquitin ligase / SCF / CAND1 / Assembly factor | |||||||||
機能・相同性 | 機能・相同性情報 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 / negative regulation of catalytic activity / PcG protein complex / cullin-RING-type E3 NEDD8 transferase / NEDD8 transferase activity / cullin-RING ubiquitin ligase complex ...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 / negative regulation of catalytic activity / PcG protein complex / cullin-RING-type E3 NEDD8 transferase / NEDD8 transferase activity / cullin-RING ubiquitin ligase complex / cellular response to chemical stress / positive regulation of ubiquitin protein ligase activity / Cul7-RING ubiquitin ligase complex / ubiquitin-dependent protein catabolic process via the C-end degron rule pathway / maintenance of protein location in nucleus / Loss of Function of FBXW7 in Cancer and NOTCH1 Signaling / positive regulation of protein autoubiquitination / protein neddylation / NEDD8 ligase activity / Cul5-RING ubiquitin ligase complex / negative regulation of response to oxidative stress / positive regulation of intracellular estrogen receptor signaling pathway / ubiquitin-ubiquitin ligase activity / SCF ubiquitin ligase complex / Cul2-RING ubiquitin ligase complex / Cul4A-RING E3 ubiquitin ligase complex / SCF-dependent proteasomal ubiquitin-dependent protein catabolic process / Cul4B-RING E3 ubiquitin ligase complex / negative regulation of type I interferon production / ubiquitin ligase complex scaffold activity / Cul3-RING ubiquitin ligase complex / Prolactin receptor signaling / protein monoubiquitination / cullin family protein binding / protein K63-linked ubiquitination / positive regulation of double-strand break repair via homologous recombination / positive regulation of RNA polymerase II transcription preinitiation complex assembly / ubiquitin-like ligase-substrate adaptor activity / protein K48-linked ubiquitination / Nuclear events stimulated by ALK signaling in cancer / ubiquitin ligase complex / TBP-class protein binding / positive regulation of TORC1 signaling / post-translational protein modification / intrinsic apoptotic signaling pathway / regulation of cellular response to insulin stimulus / Regulation of BACH1 activity / MAP3K8 (TPL2)-dependent MAPK1/3 activation / T cell activation / molecular function activator activity / SCF-beta-TrCP mediated degradation of Emi1 / NIK-->noncanonical NF-kB signaling / Vpu mediated degradation of CD4 / animal organ morphogenesis / Degradation of DVL / cellular response to amino acid stimulus / Dectin-1 mediated noncanonical NF-kB signaling / Iron uptake and transport / Recognition of DNA damage by PCNA-containing replication complex / Activation of NF-kappaB in B cells / Degradation of GLI1 by the proteasome / Negative regulation of NOTCH4 signaling / 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 / APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1 / 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 / 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 / CLEC7A (Dectin-1) signaling / SCF(Skp2)-mediated degradation of p27/p21 / beta-catenin binding / 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 / FCERI mediated NF-kB activation / Interleukin-1 signaling / Dual incision in TC-NER / Gap-filling DNA repair synthesis and ligation in TC-NER / Orc1 removal from chromatin / protein polyubiquitination / Regulation of RAS by GAPs / G1/S transition of mitotic cell cycle / positive regulation of protein catabolic process / Regulation of RUNX2 expression and activity / cellular response to UV / Cyclin D associated events in G1 / G2/M transition of mitotic cell cycle / Regulation of PLK1 Activity at G2/M Transition 類似検索 - 分子機能 | |||||||||
生物種 | Homo sapiens (ヒト) | |||||||||
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: 3.32 Å | |||||||||
データ登録者 | Baek, K. / Schulman, B.A. | |||||||||
資金援助 | ドイツ, European Union, 2件
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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 |
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-構造の表示
構造ビューア | 分子: MolmilJmol/JSmol |
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-ダウンロードとリンク
-ダウンロード
PDBx/mmCIF形式 | 8cdk.cif.gz | 411.3 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb8cdk.ent.gz | 310 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 8cdk.json.gz | ツリー表示 | PDBx/mmJSON形式 | |
その他 | その他のダウンロード |
-検証レポート
文書・要旨 | 8cdk_validation.pdf.gz | 1.1 MB | 表示 | wwPDB検証レポート |
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文書・詳細版 | 8cdk_full_validation.pdf.gz | 1.1 MB | 表示 | |
XML形式データ | 8cdk_validation.xml.gz | 69.9 KB | 表示 | |
CIF形式データ | 8cdk_validation.cif.gz | 107.2 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/cd/8cdk ftp://data.pdbj.org/pub/pdb/validation_reports/cd/8cdk | HTTPS FTP |
-関連構造データ
関連構造データ | 16576MC 7z8rC 7z8tC 7z8vC 7zbwC 7zbzC 8cdjC M: このデータのモデリングに利用したマップデータ C: 同じ文献を引用 (文献) |
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類似構造データ | 類似検索 - 機能・相同性F&H 検索 |
-リンク
-集合体
登録構造単位 |
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1 |
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-要素
-タンパク質 , 3種, 3分子 CDR
#1: タンパク質 | 分子量: 89800.367 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: CUL1 / 発現宿主: Trichoplusia ni (イラクサキンウワバ) / 参照: UniProt: Q13616 |
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#2: タンパク質 | 分子量: 137472.297 Da / 分子数: 1 / 由来タイプ: 組換発現 / 詳細: CAND1 b-hairpin++ (with M1068W P1070Q mutant) / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: CAND1, KIAA0829, TIP120, TIP120A / 発現宿主: Escherichia coli BL21(DE3) (大腸菌) / 参照: UniProt: Q86VP6 |
#3: タンパク質 | 分子量: 12089.677 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: RBX1, RNF75, ROC1 / 発現宿主: Trichoplusia ni (イラクサキンウワバ) / 参照: UniProt: P62877 |
-S-phase kinase-associated protein ... , 2種, 2分子 SF
#4: タンパク質 | 分子量: 18679.965 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: SKP1, EMC19, OCP2, SKP1A, TCEB1L / 発現宿主: Escherichia coli BL21(DE3) (大腸菌) / 参照: UniProt: P63208 |
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#5: タンパク質 | 分子量: 47961.910 Da / 分子数: 1 / 由来タイプ: 組換発現 詳細: SKP2 N-terminal region not visible in EM density. The LRR region of SKP2 was wholesale docked from previous structure with all sidechains removed. 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: SKP2, FBXL1 / 発現宿主: Escherichia coli BL21(DE3) (大腸菌) / 参照: UniProt: Q13309 |
-非ポリマー , 1種, 3分子
#6: 化合物 |
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-詳細
研究の焦点であるリガンドがあるか | Y |
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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 |
-試料調製
構成要素 | 名称: CAND1 b-hairpin++-SCF-SKP2 CAND1 partly engaged SCF partly rocked タイプ: COMPLEX / Entity ID: #1-#5 / 由来: RECOMBINANT |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
由来(組換発現) | 生物種: Escherichia coli BL21(DE3) (大腸菌) |
緩衝液 | pH: 7.5 |
試料 | 濃度: 2 mg/ml / 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 |
-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: FIELD EMISSION GUN / 加速電圧: 300 kV / 照射モード: FLOOD BEAM |
電子レンズ | モード: BRIGHT FIELD / 最大 デフォーカス(公称値): 2000 nm / 最小 デフォーカス(公称値): 500 nm |
撮影 | 電子線照射量: 68 e/Å2 フィルム・検出器のモデル: GATAN K3 BIOQUANTUM (6k x 4k) |
-解析
ソフトウェア | 名称: PHENIX / バージョン: 1.19.2_4158: / 分類: 精密化 | ||||||||||||||||||||||||
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CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3次元再構成 | 解像度: 3.32 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 62665 / 対称性のタイプ: POINT | ||||||||||||||||||||||||
拘束条件 |
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