+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-14561 | |||||||||
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Title | CAND1-CUL1-RBX1 | |||||||||
Map data | CAND1-CUL1-RBX1 RELION postprocess | |||||||||
Sample |
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Function / homology | Function and homology information SCF complex assembly / Parkin-FBXW7-Cul1 ubiquitin ligase 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 / Loss of Function of FBXW7 in Cancer and NOTCH1 Signaling ...SCF complex assembly / Parkin-FBXW7-Cul1 ubiquitin ligase 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 / 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 / SCF-dependent proteasomal ubiquitin-dependent protein catabolic process / ubiquitin-ubiquitin ligase activity / Cul4A-RING E3 ubiquitin ligase complex / Cul2-RING ubiquitin ligase complex / SCF 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 / protein K48-linked ubiquitination / positive regulation of RNA polymerase II transcription preinitiation complex assembly / 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 cell activation / 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 / Recognition of DNA damage by PCNA-containing replication complex / Dectin-1 mediated noncanonical NF-kB signaling / cellular response to amino acid stimulus / Degradation of GLI1 by the proteasome / Activation of NF-kappaB in B cells / Negative regulation of NOTCH4 signaling / Iron uptake and transport / GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2 / animal organ morphogenesis / Vif-mediated degradation of APOBEC3G / Hedgehog 'on' state / DNA Damage Recognition in GG-NER / Degradation of GLI2 by the proteasome / GLI3 is processed to GLI3R by the proteasome / G1/S transition of mitotic cell cycle / negative regulation of canonical Wnt signaling pathway / 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 / 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 / Formation of Incision Complex in GG-NER / Regulation of expression of SLITs and ROBOs / FCERI mediated NF-kB activation / Interleukin-1 signaling / Dual incision in TC-NER / protein polyubiquitination / Orc1 removal from chromatin / 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 / cellular response to UV / Cyclin D associated events in G1 / ubiquitin protein ligase activity / KEAP1-NFE2L2 pathway / Regulation of PLK1 Activity at G2/M Transition / MAPK cascade / protein-macromolecule adaptor activity / positive regulation of proteasomal ubiquitin-dependent protein catabolic process / Antigen processing: Ubiquitination & Proteasome degradation / Circadian Clock / Downstream TCR signaling / Neddylation / ubiquitin-dependent protein catabolic process / spermatogenesis / proteasome-mediated ubiquitin-dependent protein catabolic process / positive regulation of canonical NF-kappaB signal transduction / secretory granule lumen / cell population proliferation / ficolin-1-rich granule lumen / RNA polymerase II-specific DNA-binding transcription factor binding / Potential therapeutics for SARS Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.7 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_14561.map.gz | 11.2 MB | EMDB map data format | |
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Header (meta data) | emd-14561-v30.xml emd-14561.xml | 21.6 KB 21.6 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_14561_fsc.xml | 11.4 KB | Display | FSC data file |
Images | emd_14561.png | 118 KB | ||
Masks | emd_14561_msk_1.map | 125 MB | Mask map | |
Others | emd_14561_additional_1.map.gz emd_14561_additional_2.map.gz emd_14561_half_map_1.map.gz emd_14561_half_map_2.map.gz | 98.5 MB 111.6 MB 98.6 MB 98.6 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-14561 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-14561 | HTTPS FTP |
-Related structure data
Related structure data | 7z8rMC 7z8tC 7z8vC 7zbwC 7zbzC 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_14561.map.gz / Format: CCP4 / Size: 125 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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Annotation | CAND1-CUL1-RBX1 RELION postprocess | ||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
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_14561_msk_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Additional map: CAND1-CUL1-RBX1 3D Refinement
File | emd_14561_additional_1.map | ||||||||||||
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Annotation | CAND1-CUL1-RBX1 3D Refinement | ||||||||||||
Projections & Slices |
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Density Histograms |
-Additional map: CAND1-CUL1-RBX1 deepEMhancer
File | emd_14561_additional_2.map | ||||||||||||
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Annotation | CAND1-CUL1-RBX1 deepEMhancer | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: CAND1-CUL1-RBX1 halfmap1
File | emd_14561_half_map_1.map | ||||||||||||
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Annotation | CAND1-CUL1-RBX1 halfmap1 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: CAND1-CUL1-RBX1 halfmap2
File | emd_14561_half_map_2.map | ||||||||||||
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Annotation | CAND1-CUL1-RBX1 halfmap2 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : CAND1-CUL1-RBX1
Entire | Name: CAND1-CUL1-RBX1 |
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Components |
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-Supramolecule #1: CAND1-CUL1-RBX1
Supramolecule | Name: CAND1-CUL1-RBX1 / type: complex / ID: 1 / Chimera: Yes / Parent: 0 / 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: 137.386281 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 PFKHTVDDGL 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, N-terminally processed
Macromolecule | Name: E3 ubiquitin-protein ligase RBX1, N-terminally processed 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: ZINC ION
Macromolecule | Name: ZINC ION / type: ligand / ID: 4 / 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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Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy / Nominal defocus max: 2.0 µm / Nominal defocus min: 0.5 µm |
Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 60.0 e/Å2 |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |