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Yorodumi- EMDB-14597: CAND1 delhairpin-SCF-SKP2 CAND1 partly engaged SCF partly rocked -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-14597 | |||||||||
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Title | CAND1 delhairpin-SCF-SKP2 CAND1 partly engaged SCF partly rocked | |||||||||
Map data | deepEMhancer | |||||||||
Sample |
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Function / homology | Function and homology information 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 / 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 / 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 Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.1 Å | |||||||||
Authors | Baek K / Schulman BA | |||||||||
Funding support | Germany, European Union, 2 items
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Citation | Journal: Cell / Year: 2023 Title: Systemwide disassembly and assembly of SCF ubiquitin ligase complexes. Authors: Kheewoong Baek / Daniel C Scott / Lukas T Henneberg / Moeko T King / Matthias Mann / Brenda A Schulman / Abstract: 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. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_14597.map.gz | 111.6 MB | EMDB map data format | |
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Header (meta data) | emd-14597-v30.xml emd-14597.xml | 25.7 KB 25.7 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_14597_fsc.xml | 11.4 KB | Display | FSC data file |
Images | emd_14597.png | 126.7 KB | ||
Masks | emd_14597_msk_1.map | 125 MB | Mask map | |
Others | emd_14597_additional_1.map.gz emd_14597_additional_2.map.gz emd_14597_half_map_1.map.gz emd_14597_half_map_2.map.gz | 13.5 MB 98.2 MB 98.8 MB 98.4 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-14597 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-14597 | HTTPS FTP |
-Validation report
Summary document | emd_14597_validation.pdf.gz | 732 KB | Display | EMDB validaton report |
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Full document | emd_14597_full_validation.pdf.gz | 731.5 KB | Display | |
Data in XML | emd_14597_validation.xml.gz | 19 KB | Display | |
Data in CIF | emd_14597_validation.cif.gz | 24.8 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-14597 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-14597 | HTTPS FTP |
-Related structure data
Related structure data | 7zbzMC 7z8rC 7z8tC 7z8vC 7zbwC 8cdjC 8cdkC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_14597.map.gz / Format: CCP4 / Size: 125 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Annotation | deepEMhancer | ||||||||||||||||||||
Voxel size | X=Y=Z: 0.8512 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Mask #1
File | emd_14597_msk_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Additional map: relion postprocess
File | emd_14597_additional_1.map | ||||||||||||
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Annotation | relion postprocess | ||||||||||||
Projections & Slices |
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Density Histograms |
-Additional map: 3d refinement
File | emd_14597_additional_2.map | ||||||||||||
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Annotation | 3d refinement | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: halfmap1
File | emd_14597_half_map_1.map | ||||||||||||
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Annotation | halfmap1 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: halfmap2
File | emd_14597_half_map_2.map | ||||||||||||
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Annotation | halfmap2 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : CAND1 delhairpin-SCF-SKP2 CAND1 partly engaged SCF partly rocked
Entire | Name: CAND1 delhairpin-SCF-SKP2 CAND1 partly engaged SCF partly rocked |
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Components |
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-Supramolecule #1: CAND1 delhairpin-SCF-SKP2 CAND1 partly engaged SCF partly rocked
Supramolecule | Name: CAND1 delhairpin-SCF-SKP2 CAND1 partly engaged SCF partly rocked type: complex / ID: 1 / Chimera: Yes / Parent: 0 / Macromolecule list: #1-#5 |
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-Supramolecule #2: Cullin-associated NEDD8-dissociated protein 1and S-phase kinase-a...
Supramolecule | Name: Cullin-associated NEDD8-dissociated protein 1and S-phase kinase-associated protein 1 and 2 type: complex / ID: 2 / Chimera: Yes / Parent: 1 / Macromolecule list: #2, #4-#5 |
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Source (natural) | Organism: Homo sapiens (human) |
-Supramolecule #3: Cullin-1 and E3 ubiquitin-protein ligase RBX1
Supramolecule | Name: Cullin-1 and E3 ubiquitin-protein ligase RBX1 / type: complex / ID: 3 / Chimera: Yes / Parent: 1 / Macromolecule list: #1, #3 |
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Source (natural) | Organism: Homo sapiens (human) |
-Macromolecule #1: Cullin-1
Macromolecule | Name: Cullin-1 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 89.800367 KDa |
Recombinant expression | Organism: Trichoplusia ni (cabbage looper) |
Sequence | String: MSSTRSQNPH GLKQIGLDQI WDDLRAGIQQ VYTRQSMAKS RYMELYTHVY NYCTSVHQSN QARGAGVPPS KSKKGQTPGG AQFVGLELY KRLKEFLKNY LTNLLKDGED LMDESVLKFY TQQWEDYRFS SKVLNGICAY LNRHWVRREC DEGRKGIYEI Y SLALVTWR ...String: 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 |
-Macromolecule #2: Cullin-associated NEDD8-dissociated protein 1
Macromolecule | Name: Cullin-associated NEDD8-dissociated protein 1 / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 137.314156 KDa |
Recombinant expression | Organism: Escherichia coli BL21(DE3) (bacteria) |
Sequence | String: GSPEFPGRMA SASYHISNLL EKMTSSDKDF RFMATNDLMT ELQKDSIKLD DDSERKVVKM ILKLLEDKNG EVQNLAVKCL GPLVSKVKE YQVETIVDTL CTNMLSDKEQ LRDISSIGLK TVIGELPPAS SGSALAANVC KKITGRLTSA IAKQEDVSVQ L EALDIMAD ...String: 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 PFGHTVDDGL DIRKAAFECM YTLLDSCLDR LDIFEFLNHV EDG LKDHYD IKMLTFLMLV RLSTLCPSAV LQRLDRLVEP LRATCTTKVK ANSVKQEFEK QDELKRSAMR AVAALLTIPE AEKS PLMSE FQSQISSNPE LAAIFESIQK DSSSTNLESM DTS |
-Macromolecule #3: E3 ubiquitin-protein ligase RBX1
Macromolecule | Name: E3 ubiquitin-protein ligase RBX1 / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 12.089677 KDa |
Recombinant expression | Organism: Trichoplusia ni (cabbage looper) |
Sequence | String: GSMDVDTPSG TNSGAGKKRF EVKKWNAVAL WAWDIVVDNC AICRNHIMDL CIECQANQAS ATSEECTVAW GVCNHAFHFH CISRWLKTR QVCPLDNREW EFQKYGH |
-Macromolecule #4: S-phase kinase-associated protein 1
Macromolecule | Name: S-phase kinase-associated protein 1 / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 18.679965 KDa |
Recombinant expression | Organism: Escherichia coli BL21(DE3) (bacteria) |
Sequence | String: MPSIKLQSSD GEIFEVDVEI AKQSVTIKTM LEDLGMDDEG DDDPVPLPNV NAAILKKVIQ WCTHHKDDPP PPEDDENKEK RTDDIPVWD QEFLKVDQGT LFELILAANY LDIKGLLDVT CKTVANMIKG KTPEEIRKTF NIKNDFTEEE EAQVRKENQW C EEK |
-Macromolecule #5: S-phase kinase-associated protein 2
Macromolecule | Name: S-phase kinase-associated protein 2 / type: protein_or_peptide / ID: 5 Details: SKP2 N-terminal region not visible in EM density. The LRR region of SKP2 was wholesale docked from previous structure with all sidechains removed. Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 47.96191 KDa |
Recombinant expression | Organism: Escherichia coli BL21(DE3) (bacteria) |
Sequence | String: GSMHRKHLQE IPDLSSNVAT SFTWGWDSSK TSELLSGMGV SALEKEEPDS ENIPQELLSN LGHPESPPRK RLKSKGSDKD FVIVRRPKL NRENFPGVSW DSLPDELLLG IFSCLCLPEL LKVSGVCKRW YRLASDESLW QTLDLTGKNL HPDVTGRLLS Q GVIAFRCP ...String: 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 |
-Macromolecule #6: ZINC ION
Macromolecule | Name: ZINC ION / type: ligand / ID: 6 / Number of copies: 3 / Formula: ZN |
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Molecular weight | Theoretical: 65.409 Da |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 2 mg/mL |
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Buffer | pH: 7.5 |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 68.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.0 µm / Nominal defocus min: 0.5 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |