+
Open data
-
Basic information
Entry | ![]() | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Title | CAND1 b-hairpin++-SCF-SKP2 CAND1 rolling SCF engaged | |||||||||
![]() | deepEMhancer | |||||||||
![]() |
| |||||||||
Function / homology | ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() Similarity search - Function | |||||||||
Biological species | ![]() ![]() | |||||||||
Method | ![]() ![]() | |||||||||
![]() | Baek K / Schulman BA | |||||||||
Funding support | ![]()
| |||||||||
![]() | ![]() 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 |
|
-
Structure visualization
Supplemental images |
---|
-
Downloads & links
-EMDB archive
Map data | ![]() | 111.7 MB | ![]() | |
---|---|---|---|---|
Header (meta data) | ![]() ![]() | 24.1 KB 24.1 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 11.4 KB | Display | ![]() |
Images | ![]() | 136.8 KB | ||
Masks | ![]() | 125 MB | ![]() | |
Others | ![]() ![]() ![]() ![]() | 98 MB 13.6 MB 98.5 MB 98.5 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8cdjMC ![]() 7z8rC ![]() 7z8tC ![]() 7z8vC ![]() 7zbwC ![]() 7zbzC ![]() 8cdkC M: atomic model generated by this map C: citing same article ( |
---|---|
Similar structure data | Similarity search - Function & homology ![]() |
-
Links
EMDB pages | ![]() ![]() |
---|---|
Related items in Molecule of the Month |
-
Map
File | ![]() | ||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | deepEMhancer | ||||||||||||||||||||
Voxel size | X=Y=Z: 0.8512 Å | ||||||||||||||||||||
Density |
| ||||||||||||||||||||
Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
|
-Supplemental data
-Mask #1
File | ![]() | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Projections & Slices |
| ||||||||||||
Density Histograms |
-Additional map: 3d refinement
File | emd_16575_additional_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | 3d refinement | ||||||||||||
Projections & Slices |
| ||||||||||||
Density Histograms |
-Additional map: relion postprocess
File | emd_16575_additional_2.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | relion postprocess | ||||||||||||
Projections & Slices |
| ||||||||||||
Density Histograms |
-Half map: halfmap1
File | emd_16575_half_map_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | halfmap1 | ||||||||||||
Projections & Slices |
| ||||||||||||
Density Histograms |
-Half map: halfmap2
File | emd_16575_half_map_2.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | halfmap2 | ||||||||||||
Projections & Slices |
| ||||||||||||
Density Histograms |
-
Sample components
-Entire : CAND1 b-hairpin++-SCF-SKP2 CAND1 rolling SCF engaged
Entire | Name: CAND1 b-hairpin++-SCF-SKP2 CAND1 rolling SCF engaged |
---|---|
Components |
|
-Supramolecule #1: CAND1 b-hairpin++-SCF-SKP2 CAND1 rolling SCF engaged
Supramolecule | Name: CAND1 b-hairpin++-SCF-SKP2 CAND1 rolling SCF engaged / type: complex / ID: 1 / Chimera: Yes / Parent: 0 / Macromolecule list: all |
---|---|
Source (natural) | Organism: ![]() ![]() |
-Macromolecule #1: Cullin-1
Macromolecule | Name: Cullin-1 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 89.800367 KDa |
Recombinant expression | Organism: ![]() ![]() |
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: E3 ubiquitin-protein ligase RBX1, N-terminally processed
Macromolecule | Name: E3 ubiquitin-protein ligase RBX1, N-terminally processed type: protein_or_peptide / ID: 2 / Details: RING domain not visible / Number of copies: 1 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 12.089677 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: GSMDVDTPSG TNSGAGKKRF EVKKWNAVAL WAWDIVVDNC AICRNHIMDL CIECQANQAS ATSEECTVAW GVCNHAFHFH CISRWLKTR QVCPLDNREW EFQKYGH |
-Macromolecule #3: Cullin-associated NEDD8-dissociated protein 1
Macromolecule | Name: Cullin-associated NEDD8-dissociated protein 1 / type: protein_or_peptide / ID: 3 / Details: CAND1 b-hairpin++ (with M1068W P1070Q mutant) / Number of copies: 1 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 137.472297 KDa |
Recombinant expression | Organism: ![]() ![]() ![]() |
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 KELIREVEWG QFKHTVDDGL DIRKAAFECM YTLLDSCLDR LDIFEFLNHV EDG LKDHYD IKMLTFLMLV RLSTLCPSAV LQRLDRLVEP LRATCTTKVK ANSVKQEFEK QDELKRSAMR AVAALLTIPE AEKS PLMSE FQSQISSNPE LAAIFESIQK DSSSTNLESM DTS |
-Macromolecule #4: S-phase kinase-associated protein 2
Macromolecule | Name: S-phase kinase-associated protein 2 / type: protein_or_peptide / ID: 4 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 |
---|---|
Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 47.96191 KDa |
Recombinant expression | Organism: ![]() ![]() ![]() |
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 #5: S-phase kinase-associated protein 1
Macromolecule | Name: S-phase kinase-associated protein 1 / type: protein_or_peptide / ID: 5 / Number of copies: 1 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 18.679965 KDa |
Recombinant expression | Organism: ![]() ![]() ![]() |
Sequence | String: MPSIKLQSSD GEIFEVDVEI AKQSVTIKTM LEDLGMDDEG DDDPVPLPNV NAAILKKVIQ WCTHHKDDPP PPEDDENKEK RTDDIPVWD QEFLKVDQGT LFELILAANY LDIKGLLDVT CKTVANMIKG KTPEEIRKTF NIKNDFTEEE EAQVRKENQW C EEK |
-Experimental details
-Structure determination
Method | ![]() |
---|---|
![]() | ![]() |
Aggregation state | particle |
-
Sample preparation
Concentration | 2 mg/mL |
---|---|
Buffer | pH: 7.5 |
Vitrification | Cryogen name: ETHANE |
-
Electron microscopy
Microscope | FEI TITAN KRIOS |
---|---|
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD![]() |
Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 68.0 e/Å2 |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |