+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-17115 | |||||||||||||||
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タイトル | CAND1-CUL1-RBX1-DCNL1 | |||||||||||||||
マップデータ | ||||||||||||||||
試料 |
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キーワード | CAND1 / substrate receptor exchange factor / cullin-RING ligase / CRL / SCF / ligase (リガーゼ) / neddylation / DCNL1 co-E3 / ubiquitin signaling | |||||||||||||||
機能・相同性 | 機能・相同性情報 positive regulation of protein neddylation / SCF complex assembly / ubiquitin-like protein binding / Parkin-FBXW7-Cul1 ubiquitin ligase complex / regulation of protein neddylation / negative regulation of catalytic activity / cullin-RING-type E3 NEDD8 transferase / cellular response to chemical stress / NEDD8 transferase activity / cullin-RING ubiquitin ligase complex ...positive regulation of protein neddylation / SCF complex assembly / ubiquitin-like protein binding / Parkin-FBXW7-Cul1 ubiquitin ligase complex / regulation of protein neddylation / negative regulation of catalytic activity / cullin-RING-type E3 NEDD8 transferase / cellular response to chemical stress / NEDD8 transferase activity / cullin-RING ubiquitin ligase complex / Cul7-RING ubiquitin ligase complex / ubiquitin-dependent protein catabolic process via the C-end degron rule pathway / Loss of Function of FBXW7 in Cancer and NOTCH1 Signaling / positive regulation of protein autoubiquitination / protein neddylation / ubiquitin conjugating enzyme binding / NEDD8 ligase activity / Cul5-RING ubiquitin ligase complex / SCF-dependent proteasomal ubiquitin-dependent protein catabolic process / ubiquitin-ubiquitin ligase activity / Cul4A-RING E3 ubiquitin ligase complex / SCF複合体 / Cul2-RING ubiquitin ligase complex / negative regulation of type I interferon production / Cul4B-RING E3 ubiquitin ligase complex / ubiquitin ligase complex scaffold activity / Cul3-RING ubiquitin ligase complex / Prolactin receptor signaling / protein monoubiquitination / cullin family protein binding / regulation of protein ubiquitination / 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 / positive regulation of TORC1 signaling / TBP-class protein binding / Regulation of BACH1 activity / T細胞 / post-translational protein modification / MAP3K8 (TPL2)-dependent MAPK1/3 activation / intrinsic apoptotic signaling pathway / SCF-beta-TrCP mediated degradation of Emi1 / NIK-->noncanonical NF-kB signaling / Degradation of DVL / Dectin-1 mediated noncanonical NF-kB signaling / Recognition of DNA damage by PCNA-containing replication complex / cellular response to amino acid stimulus / Degradation of GLI1 by the proteasome / Activation of NF-kappaB in B cells / Negative regulation of NOTCH4 signaling / animal organ morphogenesis / Iron uptake and transport / GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2 / Vif-mediated degradation of APOBEC3G / Hedgehog 'on' state / G1/S transition of mitotic cell cycle / DNA Damage Recognition in GG-NER / 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 / RING-type E3 ubiquitin transferase / Degradation of beta-catenin by the destruction complex / Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha / negative regulation of canonical Wnt signaling pathway / Dual Incision in GG-NER / Transcription-Coupled Nucleotide Excision Repair (TC-NER) / NOTCH1 Intracellular Domain Regulates Transcription / Formation of TC-NER Pre-Incision Complex / CLEC7A (Dectin-1) signaling / SCF(Skp2)-mediated degradation of p27/p21 / 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 / protein polyubiquitination / Orc1 removal from chromatin / Dual incision in TC-NER / Gap-filling DNA repair synthesis and ligation in TC-NER / Regulation of RAS by GAPs / positive regulation of protein catabolic process / Regulation of RUNX2 expression and activity / Cyclin D associated events in G1 / cellular response to UV / ubiquitin protein ligase activity / KEAP1-NFE2L2 pathway / Regulation of PLK1 Activity at G2/M Transition / 分裂促進因子活性化タンパク質キナーゼ / protein-macromolecule adaptor activity / Antigen processing: Ubiquitination & Proteasome degradation / Circadian Clock / positive regulation of proteasomal ubiquitin-dependent protein catabolic process / Downstream TCR signaling / Neddylation / ubiquitin-dependent protein catabolic process / 精子形成 / proteasome-mediated ubiquitin-dependent protein catabolic process / secretory granule lumen 類似検索 - 分子機能 | |||||||||||||||
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: 3.2 Å | |||||||||||||||
データ登録者 | Shaaban M / Clapperton JA / Ding S / Maeots ME / Enchev RI / Maslen SL / Skehel JM | |||||||||||||||
資金援助 | 英国, 4件
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引用 | ジャーナル: Mol Cell / 年: 2023 タイトル: Structural and mechanistic insights into the CAND1-mediated SCF substrate receptor exchange. 著者: Mohammed Shaaban / Julie A Clapperton / Shan Ding / Simone Kunzelmann / Märt-Erik Mäeots / Sarah L Maslen / J Mark Skehel / Radoslav I Enchev / 要旨: Modular SCF (SKP1-CUL1-Fbox) ubiquitin E3 ligases orchestrate multiple cellular pathways in eukaryotes. Their variable SKP1-Fbox substrate receptor (SR) modules enable regulated substrate recruitment ...Modular SCF (SKP1-CUL1-Fbox) ubiquitin E3 ligases orchestrate multiple cellular pathways in eukaryotes. Their variable SKP1-Fbox substrate receptor (SR) modules enable regulated substrate recruitment and subsequent proteasomal degradation. CAND proteins are essential for the efficient and timely exchange of SRs. To gain structural understanding of the underlying molecular mechanism, we reconstituted a human CAND1-driven exchange reaction of substrate-bound SCF alongside its co-E3 ligase DCNL1 and visualized it by cryo-EM. We describe high-resolution structural intermediates, including a ternary CAND1-SCF complex, as well as conformational and compositional intermediates representing SR- or CAND1-dissociation. We describe in molecular detail how CAND1-induced conformational changes in CUL1/RBX1 provide an optimized DCNL1-binding site and reveal an unexpected dual role for DCNL1 in CAND1-SCF dynamics. Moreover, a partially dissociated CAND1-SCF conformation accommodates cullin neddylation, leading to CAND1 displacement. Our structural findings, together with functional biochemical assays, help formulate a detailed model for CAND-SCF regulation. | |||||||||||||||
履歴 |
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-構造の表示
添付画像 |
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-ダウンロードとリンク
-EMDBアーカイブ
マップデータ | emd_17115.map.gz | 110.8 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-17115-v30.xml emd-17115.xml | 20.8 KB 20.8 KB | 表示 表示 | EMDBヘッダ |
FSC (解像度算出) | emd_17115_fsc.xml | 11.3 KB | 表示 | FSCデータファイル |
画像 | emd_17115.png | 123.2 KB | ||
その他 | emd_17115_half_map_1.map.gz emd_17115_half_map_2.map.gz | 98.4 MB 98.4 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-17115 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-17115 | HTTPS FTP |
-関連構造データ
-リンク
EMDBのページ | EMDB (EBI/PDBe) / EMDataResource |
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「今月の分子」の関連する項目 |
-マップ
ファイル | ダウンロード / ファイル: emd_17115.map.gz / 形式: CCP4 / 大きさ: 125 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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ボクセルのサイズ | X=Y=Z: 1.08 Å | ||||||||||||||||||||
密度 |
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対称性 | 空間群: 1 | ||||||||||||||||||||
詳細 | EMDB XML:
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-添付データ
-ハーフマップ: #2
ファイル | emd_17115_half_map_1.map | ||||||||||||
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投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: #1
ファイル | emd_17115_half_map_2.map | ||||||||||||
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投影像・断面図 |
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密度ヒストグラム |
-試料の構成要素
-全体 : CAND1-CUL1-RBX1-DCNL1
全体 | 名称: CAND1-CUL1-RBX1-DCNL1 |
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要素 |
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-超分子 #1: CAND1-CUL1-RBX1-DCNL1
超分子 | 名称: CAND1-CUL1-RBX1-DCNL1 / タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1-#4 |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
-分子 #1: Cullin-1
分子 | 名称: Cullin-1 / タイプ: protein_or_peptide / ID: 1 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
分子量 | 理論値: 93.730672 KDa |
組換発現 | 生物種: Spodoptera frugiperda (ツマジロクサヨトウ) |
配列 | 文字列: MWSHPQFEKG SAGSAAGSGA GWSHPQFEKL EVLFQGPMSS TRSQNPHGLK QIGLDQIWDD LRAGIQQVYT RQSMAKSRYM ELYTHVYNY CTSVHQSNQA RGAGVPPSKS KKGQTPGGAQ FVGLELYKRL KEFLKNYLTN LLKDGEDLMD ESVLKFYTQQ W EDYRFSSK ...文字列: MWSHPQFEKG SAGSAAGSGA GWSHPQFEKL EVLFQGPMSS TRSQNPHGLK QIGLDQIWDD LRAGIQQVYT RQSMAKSRYM ELYTHVYNY CTSVHQSNQA RGAGVPPSKS KKGQTPGGAQ FVGLELYKRL KEFLKNYLTN LLKDGEDLMD ESVLKFYTQQ W EDYRFSSK VLNGICAYLN RHWVRRECDE GRKGIYEIYS LALVTWRDCL FRPLNKQVTN AVLKLIEKER NGETINTRLI SG VVQSYVE LGLNEDDAFA KGPTLTVYKE SFESQFLADT ERFYTRESTE FLQQNPVTEY MKKAEARLLE EQRRVQVYLH EST QDELAR KCEQVLIEKH LEIFHTEFQN LLDADKNEDL GRMYNLVSRI QDGLGELKKL LETHIHNQGL AAIEKCGEAA LNDP KMYVQ TVLDVHKKYN ALVMSAFNND AGFVAALDKA CGRFINNNAV TKMAQSSSKS PELLARYCDS LLKKSSKNPE EAELE DTLN QVMVVFKYIE DKDVFQKFYA KMLAKRLVHQ NSASDDAEAS MISKLKQACG FEYTSKLQRM FQDIGVSKDL NEQFKK HLT NSEPLDLDFS IQVLSSGSWP FQQSCTFALP SELERSYQRF TAFYASRHSG RKLTWLYQLS KGELVTNCFK NRYTLQA ST FQMAILLQYN TEDAYTVQQL TDSTQIKMDI LAQVLQILLK SKLLVLEDEN ANVDEVELKP DTLIKLYLGY KNKKLRVN I NVPMKTEQKQ EQETTHKNIE EDRKLLIQAA IVRIMKMRKV LKHQQLLGEV LTQLSSRFKP RVPVIKKCID ILIEKEYLE RVDGEKDTYS YLA UniProtKB: Cullin-1 |
-分子 #2: E3 ubiquitin-protein ligase RBX1
分子 | 名称: E3 ubiquitin-protein ligase RBX1 / タイプ: protein_or_peptide / ID: 2 / コピー数: 1 / 光学異性体: LEVO / EC番号: RING-type E3 ubiquitin transferase |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
分子量 | 理論値: 12.289977 KDa |
組換発現 | 生物種: Spodoptera frugiperda (ツマジロクサヨトウ) |
配列 | 文字列: MAAAMDVDTP SGTNSGAGKK RFEVKKWNAV ALWAWDIVVD NCAICRNHIM DLCIECQANQ ASATSEECTV AWGVCNHAFH FHCISRWLK TRQVCPLDNR EWEFQKYGH UniProtKB: E3 ubiquitin-protein ligase RBX1 |
-分子 #3: Cullin-associated NEDD8-dissociated protein 1
分子 | 名称: Cullin-associated NEDD8-dissociated protein 1 / タイプ: protein_or_peptide / ID: 3 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
分子量 | 理論値: 137.358219 KDa |
組換発現 | 生物種: Escherichia coli BL21(DE3) (大腸菌) |
配列 | 文字列: GSPEFPGRMA SASYHISNLL EKMTSSDKDF RFMATNDLMT ELQKDSIKLD DDSERKVVKM ILKLLEDKNG EVQNLAVKCL GPLVSKVKE YQVETIVDTL CTNMLSDKEQ LRDISSIGLK TVIGELPPAS SGSALAANVC KKITGRLTSA IAKQEDVSVQ L EALDIMAD ...文字列: GSPEFPGRMA SASYHISNLL EKMTSSDKDF RFMATNDLMT ELQKDSIKLD DDSERKVVKM ILKLLEDKNG EVQNLAVKCL GPLVSKVKE YQVETIVDTL CTNMLSDKEQ LRDISSIGLK TVIGELPPAS SGSALAANVC KKITGRLTSA IAKQEDVSVQ L EALDIMAD MLSRQGGLLV NFHPSILTCL LPQLTSPRLA VRKRTIIALG HLVMSCGNIV FVDLIEHLLS ELSKNDSMST TR TYIQCIA AISRQAGHRI GEYLEKIIPL VVKFCNVDDD ELREYCIQAF ESFVRRCPKE VYPHVSTIIN ICLKYLTYDP NYN YDDEDE DENAMDADGG DDDDQGSDDE YSDDDDMSWK VRRAAAKCLD AVVSTRHEML PEFYKTVSPA LISRFKEREE NVKA DVFHA YLSLLKQTRP VQSWLCDPDA MEQGETPLTM LQSQVPNIVK ALHKQMKEKS VKTRQCCFNM LTELVNVLPG ALTQH IPVL VPGIIFSLND KSSSSNLKID ALSCLYVILC NHSPQVFHPH VQALVPPVVA CVGDPFYKIT SEALLVTQQL VKVIRP LDQ PSSFDATPYI KDLFTCTIKR LKAADIDQEV KERAISCMGQ IICNLGDNLG SDLPNTLQIF LERLKNEITR LTTVKAL TL IAGSPLKIDL RPVLGEGVPI LASFLRKNQR ALKLGTLSAL DILIKNYSDS LTAAMIDAVL DELPPLISES DMHVSQMA I SFLTTLAKVY PSSLSKISGS ILNELIGLVR SPLLQGGALS AMLDFFQALV VTGTNNLGYM DLLRMLTGPV YSQSTALTH KQSYYSIAKC VAALTRACPK EGPAVVGQFI QDVKNSRSTD SIRLLALLSL GEVGHHIDLS GQLELKSVIL EAFSSPSEEV KSAASYALG SISVGNLPEY LPFVLQEITS QPKRQYLLLH SLKEIISSAS VVGLKPYVEN IWALLLKHCE CAEEGTRNVV A ECLGKLTL IDPETLLPRL KGYLISGSSY ARSSVVTAVK FTISDHPQPI DPLLKNCIGD FLKTLEDPDL NVRRVALVTF NS AAHNKPS LIRDLLDTVL PHLYNETKVR KELIREVEMG PFKHTVDDGL DIRKAAFECM YTLLDSCLDR LDIFEFLNHV EDG LKDHYD IKMLTFLMLV RLSTLCPSAV LQRLDRLVEP LRATCTTKVK ANSVKQEFEK QDELKRSAMR AVAALLTIPE AEKS PLMSE FQSQISSNPE LAAIFESIQK DSSSTNLESM DTS UniProtKB: Cullin-associated NEDD8-dissociated protein 1 |
-分子 #4: DCN1-like protein 1
分子 | 名称: DCN1-like protein 1 / タイプ: protein_or_peptide / ID: 4 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
分子量 | 理論値: 30.304439 KDa |
組換発現 | 生物種: Escherichia coli BL21(DE3) (大腸菌) |
配列 | 文字列: GSMNKLKSSQ KDKVRQFMIF TQSSEKTAVS CLSQNDWKLD VATDNFFQNP ELYIRESVKG SLDRKKLEQL YNRYKDPQDE NKIGIDGIQ QFCDDLALDP ASISVLIIAW KFRAATQCEF SKQEFMDGMT ELGCDSIEKL KAQIPKMEQE LKEPGRFKDF Y QFTFNFAK ...文字列: GSMNKLKSSQ KDKVRQFMIF TQSSEKTAVS CLSQNDWKLD VATDNFFQNP ELYIRESVKG SLDRKKLEQL YNRYKDPQDE NKIGIDGIQ QFCDDLALDP ASISVLIIAW KFRAATQCEF SKQEFMDGMT ELGCDSIEKL KAQIPKMEQE LKEPGRFKDF Y QFTFNFAK NPGQKGLDLE MAIAYWNLVL NGRFKFLDLW NKFLLEHHKR SIPKDTWNLL LDFSTMIADD MSNYDEEGAW PV LIDDFVE FARPQIAGTK STTV UniProtKB: DCN1-like protein 1 |
-分子 #5: ZINC ION
分子 | 名称: ZINC ION / タイプ: ligand / ID: 5 / コピー数: 3 / 式: ZN |
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分子量 | 理論値: 65.409 Da |
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
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解析 | 単粒子再構成法 |
試料の集合状態 | particle |
-試料調製
緩衝液 | pH: 7.5 構成要素:
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凍結 | 凍結剤: ETHANE / チャンバー内湿度: 100 % / チャンバー内温度: 277.15 K / 装置: FEI VITROBOT MARK IV | ||||||||||
詳細 | CAND1-CUL1-RBX1-SKP1-SKP2-CKS1-CDK2-CyclinE-DCNL1 |
-電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
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電子線 | 加速電圧: 300 kV / 電子線源: FIELD EMISSION GUN |
電子光学系 | 照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELDBright-field microscopy / 最大 デフォーカス(公称値): 2.5 µm 最小 デフォーカス(公称値): 0.7000000000000001 µm 倍率(公称値): 130000 |
撮影 | フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) 平均電子線量: 49.1 e/Å2 |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |