+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-14594 | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
タイトル | CAND1-SCF-SKP2 CAND1 rolling-2 SCF engaged | |||||||||
マップデータ | CAND1-SCFSKP2 Class1 deepEMhancer | |||||||||
試料 |
| |||||||||
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 / PcG protein complex / negative regulation of catalytic activity / cullin-RING-type E3 NEDD8 transferase / cellular response to chemical stress / NEDD8 transferase 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-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 / 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 / negative regulation of response to oxidative stress / 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 / negative regulation of type I interferon production / 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 / positive regulation of TORC1 signaling / T cell activation / TBP-class protein binding / Regulation of BACH1 activity / intrinsic apoptotic signaling pathway / MAP3K8 (TPL2)-dependent MAPK1/3 activation / post-translational protein modification / SCF-beta-TrCP mediated degradation of Emi1 / NIK-->noncanonical NF-kB signaling / molecular function activator activity / Vpu mediated degradation of CD4 / Degradation of DVL / Dectin-1 mediated noncanonical NF-kB signaling / Recognition of DNA damage by PCNA-containing replication complex / Degradation of GLI1 by the proteasome / Activation of NF-kappaB in B cells / animal organ morphogenesis / Negative regulation of NOTCH4 signaling / cellular response to amino acid stimulus / Iron uptake and transport / 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 / DNA Damage Recognition in GG-NER / 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 / RING-type E3 ubiquitin transferase / Degradation of beta-catenin by the destruction complex / negative regulation of canonical Wnt signaling pathway / Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha / Dual Incision in GG-NER / Evasion by RSV of host interferon responses / NOTCH1 Intracellular Domain Regulates Transcription / Transcription-Coupled Nucleotide Excision Repair (TC-NER) / Formation of TC-NER Pre-Incision Complex / CLEC7A (Dectin-1) signaling / SCF(Skp2)-mediated degradation of p27/p21 / beta-catenin binding / Regulation of expression of SLITs and ROBOs / Constitutive Signaling by NOTCH1 PEST Domain Mutants / Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants / Formation of Incision Complex in GG-NER / FCERI mediated NF-kB activation / Interleukin-1 signaling / Orc1 removal from chromatin / Dual incision in TC-NER / G1/S transition of mitotic cell cycle / Gap-filling DNA repair synthesis and ligation in TC-NER / Regulation of RAS by GAPs / protein polyubiquitination / positive regulation of protein catabolic process / G2/M transition of mitotic cell cycle / Regulation of RUNX2 expression and activity / Cyclin D associated events in G1 / cellular response to UV / Regulation of PLK1 Activity at G2/M Transition / KEAP1-NFE2L2 pathway 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: 3.5 Å | |||||||||
データ登録者 | Baek K / Schulman BA | |||||||||
資金援助 | ドイツ, European Union, 2件
| |||||||||
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 |
|
-構造の表示
添付画像 |
---|
-ダウンロードとリンク
-EMDBアーカイブ
マップデータ | emd_14594.map.gz | 111.5 MB | EMDBマップデータ形式 | |
---|---|---|---|---|
ヘッダ (付随情報) | emd-14594-v30.xml emd-14594.xml | 24 KB 24 KB | 表示 表示 | EMDBヘッダ |
FSC (解像度算出) | emd_14594_fsc.xml | 11.4 KB | 表示 | FSCデータファイル |
画像 | emd_14594.png | 163.6 KB | ||
マスクデータ | emd_14594_msk_1.map | 125 MB | マスクマップ | |
その他 | emd_14594_additional_1.map.gz emd_14594_additional_2.map.gz emd_14594_half_map_1.map.gz emd_14594_half_map_2.map.gz | 98.5 MB 12.9 MB 98.6 MB 98.5 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-14594 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-14594 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_14594_validation.pdf.gz | 758.1 KB | 表示 | EMDB検証レポート |
---|---|---|---|---|
文書・詳細版 | emd_14594_full_validation.pdf.gz | 757.7 KB | 表示 | |
XML形式データ | emd_14594_validation.xml.gz | 19 KB | 表示 | |
CIF形式データ | emd_14594_validation.cif.gz | 24.7 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-14594 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-14594 | HTTPS FTP |
-関連構造データ
関連構造データ | 7zbwMC 7z8rC 7z8tC 7z8vC 7zbzC 8cdjC 8cdkC M: このマップから作成された原子モデル C: 同じ文献を引用 (文献) |
---|---|
類似構造データ | 類似検索 - 機能・相同性F&H 検索 |
-リンク
EMDBのページ | EMDB (EBI/PDBe) / EMDataResource |
---|---|
「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_14594.map.gz / 形式: CCP4 / 大きさ: 125 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
注釈 | CAND1-SCFSKP2 Class1 deepEMhancer | ||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 0.8512 Å | ||||||||||||||||||||
密度 |
| ||||||||||||||||||||
対称性 | 空間群: 1 | ||||||||||||||||||||
詳細 | EMDB XML:
|
-添付データ
-マスク #1
ファイル | emd_14594_msk_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
投影像・断面図 |
| ||||||||||||
密度ヒストグラム |
-追加マップ: CAND1-SCFSKP2 Class1 3D Refinement
ファイル | emd_14594_additional_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
注釈 | CAND1-SCFSKP2 Class1 3D Refinement | ||||||||||||
投影像・断面図 |
| ||||||||||||
密度ヒストグラム |
-追加マップ: CAND1-SCFSKP2 Class1 RELION postprocess
ファイル | emd_14594_additional_2.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
注釈 | CAND1-SCFSKP2 Class1 RELION postprocess | ||||||||||||
投影像・断面図 |
| ||||||||||||
密度ヒストグラム |
-ハーフマップ: CAND1-SCFSKP2 Class1 halfmap2
ファイル | emd_14594_half_map_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
注釈 | CAND1-SCFSKP2 Class1 halfmap2 | ||||||||||||
投影像・断面図 |
| ||||||||||||
密度ヒストグラム |
-ハーフマップ: CAND1-SCFSKP2 Class1 halfmap1
ファイル | emd_14594_half_map_2.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
注釈 | CAND1-SCFSKP2 Class1 halfmap1 | ||||||||||||
投影像・断面図 |
| ||||||||||||
密度ヒストグラム |
-試料の構成要素
-全体 : CAND1-SCF-SKP2 CAND1 rolling-2 SCF engaged
全体 | 名称: CAND1-SCF-SKP2 CAND1 rolling-2 SCF engaged |
---|---|
要素 |
|
-超分子 #1: CAND1-SCF-SKP2 CAND1 rolling-2 SCF engaged
超分子 | 名称: CAND1-SCF-SKP2 CAND1 rolling-2 SCF engaged / タイプ: complex / ID: 1 / キメラ: Yes / 親要素: 0 / 含まれる分子: all |
---|---|
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 |
---|---|
由来(天然) | 生物種: Homo sapiens (ヒト) |
分子量 | 理論値: 89.800367 KDa |
組換発現 | 生物種: Trichoplusia ni (イラクサキンウワバ) |
配列 | 文字列: MSSTRSQNPH GLKQIGLDQI WDDLRAGIQQ VYTRQSMAKS RYMELYTHVY NYCTSVHQSN QARGAGVPPS KSKKGQTPGG AQFVGLELY KRLKEFLKNY LTNLLKDGED LMDESVLKFY TQQWEDYRFS SKVLNGICAY LNRHWVRREC DEGRKGIYEI Y SLALVTWR ...文字列: MSSTRSQNPH GLKQIGLDQI WDDLRAGIQQ VYTRQSMAKS RYMELYTHVY NYCTSVHQSN QARGAGVPPS KSKKGQTPGG AQFVGLELY KRLKEFLKNY LTNLLKDGED LMDESVLKFY TQQWEDYRFS SKVLNGICAY LNRHWVRREC DEGRKGIYEI Y SLALVTWR DCLFRPLNKQ VTNAVLKLIE KERNGETINT RLISGVVQSY VELGLNEDDA FAKGPTLTVY KESFESQFLA DT ERFYTRE STEFLQQNPV TEYMKKAEAR LLEEQRRVQV YLHESTQDEL ARKCEQVLIE KHLEIFHTEF QNLLDADKNE DLG RMYNLV SRIQDGLGEL KKLLETHIHN QGLAAIEKCG EAALNDPKMY VQTVLDVHKK YNALVMSAFN NDAGFVAALD KACG RFINN NAVTKMAQSS SKSPELLARY CDSLLKKSSK NPEEAELEDT LNQVMVVFKY IEDKDVFQKF YAKMLAKRLV HQNSA SDDA EASMISKLKQ ACGFEYTSKL QRMFQDIGVS KDLNEQFKKH LTNSEPLDLD FSIQVLSSGS WPFQQSCTFA LPSELE RSY QRFTAFYASR HSGRKLTWLY QLSKGELVTN CFKNRYTLQA STFQMAILLQ YNTEDAYTVQ QLTDSTQIKM DILAQVL QI LLKSKLLVLE DENANVDEVE LKPDTLIKLY LGYKNKKLRV NINVPMKTEQ KQEQETTHKN IEEDRKLLIQ AAIVRIMK M RKVLKHQQLL GEVLTQLSSR FKPRVPVIKK CIDILIEKEY LERVDGEKDT YSYLA |
-分子 #2: E3 ubiquitin-protein ligase RBX1, N-terminally processed
分子 | 名称: E3 ubiquitin-protein ligase RBX1, N-terminally processed タイプ: protein_or_peptide / ID: 2 / コピー数: 1 / 光学異性体: LEVO |
---|---|
由来(天然) | 生物種: Homo sapiens (ヒト) |
分子量 | 理論値: 12.089677 KDa |
組換発現 | 生物種: Trichoplusia ni (イラクサキンウワバ) |
配列 | 文字列: GSMDVDTPSG TNSGAGKKRF EVKKWNAVAL WAWDIVVDNC AICRNHIMDL CIECQANQAS ATSEECTVAW GVCNHAFHFH CISRWLKTR QVCPLDNREW EFQKYGH |
-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 |
---|---|
由来(天然) | 生物種: Homo sapiens (ヒト) |
分子量 | 理論値: 137.386281 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 V 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 |
-分子 #4: S-phase kinase-associated protein 2
分子 | 名称: S-phase kinase-associated protein 2 / タイプ: protein_or_peptide / ID: 4 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. コピー数: 1 / 光学異性体: LEVO |
---|---|
由来(天然) | 生物種: Homo sapiens (ヒト) |
分子量 | 理論値: 47.96191 KDa |
組換発現 | 生物種: Escherichia coli BL21(DE3) (大腸菌) |
配列 | 文字列: GSMHRKHLQE IPDLSSNVAT SFTWGWDSSK TSELLSGMGV SALEKEEPDS ENIPQELLSN LGHPESPPRK RLKSKGSDKD FVIVRRPKL NRENFPGVSW DSLPDELLLG IFSCLCLPEL LKVSGVCKRW YRLASDESLW QTLDLTGKNL HPDVTGRLLS Q GVIAFRCP ...文字列: GSMHRKHLQE IPDLSSNVAT SFTWGWDSSK TSELLSGMGV SALEKEEPDS ENIPQELLSN LGHPESPPRK RLKSKGSDKD FVIVRRPKL NRENFPGVSW DSLPDELLLG IFSCLCLPEL LKVSGVCKRW YRLASDESLW QTLDLTGKNL HPDVTGRLLS Q GVIAFRCP RSFMDQPLAE HFSPFRVQHM DLSNSVIEVS TLHGILSQCS KLQNLSLEGL RLSDPIVNTL AKNSNLVRLN LS GCSGFSE FALQTLLSSC SRLDELNLSW CFDFTEKHVQ VAVAHVSETI TQLNLSGYRK NLQKSDLSTL VRRCPNLVHL DLS DSVMLK NDCFQEFFQL NYLQHLSLSR CYDIIPETLL ELGEIPTLKT LQVFGIVPDG TLQLLKEALP HLQINCSHFT TIAR PTIGN KKNQEIWGIK CRLTLQKPSC L |
-分子 #5: S-phase kinase-associated protein 1
分子 | 名称: S-phase kinase-associated protein 1 / タイプ: protein_or_peptide / ID: 5 / コピー数: 1 / 光学異性体: LEVO |
---|---|
由来(天然) | 生物種: Homo sapiens (ヒト) |
分子量 | 理論値: 18.679965 KDa |
組換発現 | 生物種: Escherichia coli BL21(DE3) (大腸菌) |
配列 | 文字列: MPSIKLQSSD GEIFEVDVEI AKQSVTIKTM LEDLGMDDEG DDDPVPLPNV NAAILKKVIQ WCTHHKDDPP PPEDDENKEK RTDDIPVWD QEFLKVDQGT LFELILAANY LDIKGLLDVT CKTVANMIKG KTPEEIRKTF NIKNDFTEEE EAQVRKENQW C EEK |
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
---|---|
解析 | 単粒子再構成法 |
試料の集合状態 | particle |
-試料調製
濃度 | 2 mg/mL |
---|---|
緩衝液 | pH: 7.5 |
凍結 | 凍結剤: ETHANE |
-電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
---|---|
撮影 | フィルム・検出器のモデル: GATAN K3 BIOQUANTUM (6k x 4k) 平均電子線量: 68.0 e/Å2 |
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 FIELD / 最大 デフォーカス(公称値): 2.0 µm / 最小 デフォーカス(公称値): 0.5 µm |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |