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- EMDB-18214: Structure of CUL9-RBX1 ubiquitin E3 ligase complex - hexameric as... -
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Basic information
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Title | Structure of CUL9-RBX1 ubiquitin E3 ligase complex - hexameric assembly | |||||||||
![]() | postprocess map | |||||||||
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![]() | Cullin-RING RBR E3 Ligase / LIGASE | |||||||||
Function / homology | ![]() 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 ...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 / negative regulation of response to oxidative stress / ubiquitin-ubiquitin ligase activity / Cul4A-RING E3 ubiquitin ligase complex / SCF ubiquitin ligase complex / Cul2-RING ubiquitin ligase complex / regulation of mitotic nuclear division / Cul4B-RING E3 ubiquitin ligase complex / negative regulation of type I interferon production / SCF-dependent proteasomal ubiquitin-dependent protein catabolic process / Cul3-RING ubiquitin ligase complex / Prolactin receptor signaling / protein monoubiquitination / cullin family protein binding / protein K48-linked ubiquitination / Nuclear events stimulated by ALK signaling in cancer / positive regulation of TORC1 signaling / T cell activation / regulation of cellular response to insulin stimulus / Regulation of BACH1 activity / post-translational protein modification / Degradation of DVL / Recognition of DNA damage by PCNA-containing replication complex / Degradation of GLI1 by the proteasome / Negative regulation of NOTCH4 signaling / cellular response to amino acid stimulus / 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 / FBXL7 down-regulates AURKA during mitotic entry and in early mitosis / DNA Damage Recognition in GG-NER / RING-type E3 ubiquitin transferase / negative regulation of canonical Wnt signaling pathway / Degradation of beta-catenin by the destruction complex / Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha / Transcription-Coupled Nucleotide Excision Repair (TC-NER) / Formation of TC-NER Pre-Incision Complex / Dual Incision in GG-NER / Evasion by RSV of host interferon responses / NOTCH1 Intracellular Domain Regulates Transcription / 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 / microtubule cytoskeleton organization / Dual incision in TC-NER / Interleukin-1 signaling / Orc1 removal from chromatin / Gap-filling DNA repair synthesis and ligation in TC-NER / Regulation of RAS by GAPs / protein polyubiquitination / positive regulation of protein catabolic process / Regulation of RUNX2 expression and activity / cellular response to UV / MAPK cascade / ubiquitin protein ligase activity / KEAP1-NFE2L2 pathway / positive regulation of proteasomal ubiquitin-dependent protein catabolic process / Antigen processing: Ubiquitination & Proteasome degradation / Neddylation / ubiquitin-dependent protein catabolic process / spermatogenesis / proteasome-mediated ubiquitin-dependent protein catabolic process / positive regulation of canonical NF-kappaB signal transduction / RNA polymerase II-specific DNA-binding transcription factor binding / Potential therapeutics for SARS / molecular adaptor activity / protein ubiquitination / DNA repair / ubiquitin protein ligase binding / DNA damage response / zinc ion binding / nucleoplasm / ATP binding / nucleus / cytosol / cytoplasm Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 4.4 Å | |||||||||
![]() | Hopf LVM / Horn-Ghetko D / Schulman BA | |||||||||
Funding support | European Union, ![]()
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![]() | ![]() Title: Noncanonical assembly, neddylation and chimeric cullin-RING/RBR ubiquitylation by the 1.8 MDa CUL9 E3 ligase complex. Authors: Daniel Horn-Ghetko / Linus V M Hopf / Ishita Tripathi-Giesgen / Jiale Du / Sebastian Kostrhon / D Tung Vu / Viola Beier / Barbara Steigenberger / J Rajan Prabu / Luca Stier / Elias M Bruss / ...Authors: Daniel Horn-Ghetko / Linus V M Hopf / Ishita Tripathi-Giesgen / Jiale Du / Sebastian Kostrhon / D Tung Vu / Viola Beier / Barbara Steigenberger / J Rajan Prabu / Luca Stier / Elias M Bruss / Matthias Mann / Yue Xiong / Brenda A Schulman / ![]() ![]() Abstract: Ubiquitin ligation is typically executed by hallmark E3 catalytic domains. Two such domains, 'cullin-RING' and 'RBR', are individually found in several hundred human E3 ligases, and collaborate with ...Ubiquitin ligation is typically executed by hallmark E3 catalytic domains. Two such domains, 'cullin-RING' and 'RBR', are individually found in several hundred human E3 ligases, and collaborate with E2 enzymes to catalyze ubiquitylation. However, the vertebrate-specific CUL9 complex with RBX1 (also called ROC1), of interest due to its tumor suppressive interaction with TP53, uniquely encompasses both cullin-RING and RBR domains. Here, cryo-EM, biochemistry and cellular assays elucidate a 1.8-MDa hexameric human CUL9-RBX1 assembly. Within one dimeric subcomplex, an E2-bound RBR domain is activated by neddylation of its own cullin domain and positioning from the adjacent CUL9-RBX1 in trans. Our data show CUL9 as unique among RBX1-bound cullins in dependence on the metazoan-specific UBE2F neddylation enzyme, while the RBR domain protects it from deneddylation. Substrates are recruited to various upstream domains, while ubiquitylation relies on both CUL9's neddylated cullin and RBR domains achieving self-assembled and chimeric cullin-RING/RBR E3 ligase activity. | |||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 57.9 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 21.7 KB 21.7 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 17.9 KB | Display | ![]() |
Images | ![]() | 78.3 KB | ||
Masks | ![]() | 488.4 MB | ![]() | |
Filedesc metadata | ![]() | 7.2 KB | ||
Others | ![]() ![]() ![]() | 388 MB 388 MB 388.1 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8q7eMC ![]() 8q7hC ![]() 8rhzC C: citing same article ( M: atomic model generated by this map |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Annotation | postprocess map | ||||||||||||||||||||
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
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-Additional map: refinement map
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Annotation | refinement map | ||||||||||||
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-Half map: #2
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-Half map: #1
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Sample components
-Entire : Structure of CUL9-RBX1 ubiquitin E3 ligase complex - hexameric as...
Entire | Name: Structure of CUL9-RBX1 ubiquitin E3 ligase complex - hexameric assembly |
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Components |
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-Supramolecule #1: Structure of CUL9-RBX1 ubiquitin E3 ligase complex - hexameric as...
Supramolecule | Name: Structure of CUL9-RBX1 ubiquitin E3 ligase complex - hexameric assembly type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: ![]() |
-Macromolecule #1: Cullin-9
Macromolecule | Name: Cullin-9 / type: protein_or_peptide / ID: 1 / Number of copies: 6 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 281.531875 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MVGERHAGDL MVPLGPRLQA YPEELIRQRP GHDGHPEYLI RWSVLKCGEV GKVGVEEGKA EHILMWLSAP EVYANCPGLL GERALSKGL QHEPAGVSGS FPRDPGGLDE VAMGEMEADV QALVRRAARQ LAESGTPSLT AAVLHTIHVL SAYASIGPLT G VFRETGAL ...String: MVGERHAGDL MVPLGPRLQA YPEELIRQRP GHDGHPEYLI RWSVLKCGEV GKVGVEEGKA EHILMWLSAP EVYANCPGLL GERALSKGL QHEPAGVSGS FPRDPGGLDE VAMGEMEADV QALVRRAARQ LAESGTPSLT AAVLHTIHVL SAYASIGPLT G VFRETGAL DLLMHMLCNP EPQIRRSAGK MLQALAAHDA GSRAHVLLSL SQQDGIEQHM DFDSRYTLLE LFAETTSSEE HC MAFEGIH LPQIPGKLLF SLVKRYLCVT SLLDQLNSSP ELGAGDQSSP CATREKSRGQ RELEFSMAVG NLISELVRSM GWA RNLSEQ GMSPPRPTRS IFQPYISGPS LLLPTIVTTP RRQGWVFRQR SEFSSRSGYG EYVQQTLQPG MRVRMLDDYE EISA GDEGE FRQSNNGIPP VQVFWQSTGR TYWVHWHMLE ILGPEEATED KASAAVEKGA GATVLGTAFP SWDWNPMDGL YPLPY LQPE PQKNERVGYL TQAEWWELLF FIKKLDLCEQ QPIFQNLWKN LDETLGEKAL GEISVSVEMA ESLLQVLSSR FEGSTL NDL LNSQIYTKYG LLSNEPSSSS TSRNHSCTPD PEEESKSEAS FSEEETESLK AKAEAPKTEA EPTKTRTETP MAQSDSQ LF NQLLVTEGMT LPTEMKEAAS EMARALRGPG PRSSLDQHVA AVVATVQISS LDTNLQLSGL SALSQAVEEV TERDHPLV R PDRSLREKLV KMLVELLTNQ VGEKMVVVQA LRLLYLLMTK HEWRPLFARE GGIYAVLVCM QEYKTSVLVQ QAGLAALKM LAVASSSEIP TFVTGRDSIH SLFDAQMTRE IFASIDSATR PGSESLLLTV PAAVILMLNT EGCSSAARNG LLLLNLLLCN HHTLGDQII TQELRDTLFR HSGIAPRTEP MPTTRTILMM LLNRYSEPPG SPERAALETP IIQGQDGSPE LLIRSLVGGP S AELLLDLE RVLCREGSPG GAVRPLLKRL QQETQPFLLL LRTLDAPGPN KTLLLSVLRV ITRLLDFPEA MVLPWHEVLE PC LNCLSGP SSDSEIVQEL TCFLHRLASM HKDYAVVLCC LGAKEILSKV LDKHSAQLLL GCELRDLVTE CEKYAQLYSN LTS SILAGC IQMVLGQIED HRRTHQPINI PFFDVFLRHL CQGSSVEVKE DKCWEKVEVS SNPHRASKLT DHNPKTYWES NGST GSHYI TLHMHRGVLV RQLTLLVASE DSSYMPARVV VFGGDSTSCI GTELNTVNVM PSASRVILLE NLNRFWPIIQ IRIKR CQQG GIDTRVRGVE VLGPKPTFWP LFREQLCRRT CLFYTIRAQA WSRDIAEDHR RLLQLCPRLN RVLRHEQNFA DRFLPD DEA AQALGKTCWE ALVSPLVQNI TSPDAEGVSA LGWLLDQYLE QRETSRNPLS RAASFASRVR RLCHLLVHVE PPPGPSP EP STRPFSKNSK GRDRSPAPSP VLPSSSLRNI TQCWLSVVQE QVSRFLAAAW RAPDFVPRYC KLYEHLQRAG SELFGPRA A FMLALRSGFS GALLQQSFLT AAHMSEQFAR YIDQQIQGGL IGGAPGVEML GQLQRHLEPI MVLSGLELAT TFEHFYQHY MADRLLSFGS SWLEGAVLEQ IGLCFPNRLP QLMLQSLSTS EELQRQFHLF QLQRLDKLFL EQEDEEEKRL EEEEEEEEEE EAEKELFIE DPSPAISILV LSPRCWPVSP LCYLYHPRKC LPTEFCDALD RFSSFYSQSQ NHPVLDMGPH RRLQWTWLGR A ELQFGKQI LHVSTVQMWL LLKFNQTEEV SVETLLKDSD LSPELLLQAL VPLTSGNGPL TLHEGQDFPH GGVLRLHEPG PQ RSGEALW LIPPQAYLNV EKDEGRTLEQ KRNLLSCLLV RILKAHGEKG LHIDQLVCLV LEAWQKGPNP PGTLGHTVAG GVA CTSTDV LSCILHLLGQ GYVKRRDDRP QILMYAAPEP MGPCRGQADV PFCGSQSETS KPSPEAVATL ASLQLPAGRT MSPQ EVEGL MKQTVRQVQE TLNLEPDVAQ HLLAHSHWGA EQLLQSYSED PEPLLLAAGL CVHQAQAVPV RPDHCPVCVS PLGCD DDLP SLCCMHYCCK SCWNEYLTTR IEQNLVLNCT CPIADCPAQP TGAFIRAIVS SPEVISKYEK ALLRGYVESC SNLTWC TNP QGCDRILCRQ GLGCGTTCSK CGWASCFNCS FPEAHYPASC GHMSQWVDDG GYYDGMSVEA QSKHLAKLIS KRCPSCQ AP IEKNEGCLHM TCAKCNHGFC WRCLKSWKPN HKDYYNCSAM VSKAARQEKR FQDYNERCTF HHQAREFAVN LRNRVSAI H EVPPPRSFTF LNDACQGLEQ ARKVLAYACV YSFYSQDAEY MDVVEQQTEN LELHTNALQI LLEETLLRCR DLASSLRLL RADCLSTGME LLRRIQERLL AILQHSAQDF RVGLQSPSVE AWEAKGPNMP GSQPQASSGP EAEEEEEDDE DDVPEWQQDE FDEELDNDS FSYDESENLD QETFFFGDEE EDEDEAYD UniProtKB: Cullin-9 |
-Macromolecule #2: E3 ubiquitin-protein ligase RBX1
Macromolecule | Name: E3 ubiquitin-protein ligase RBX1 / type: protein_or_peptide / ID: 2 / Number of copies: 6 / Enantiomer: LEVO / EC number: RING-type E3 ubiquitin transferase |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 12.289977 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MAAAMDVDTP SGTNSGAGKK RFEVKKWNAV ALWAWDIVVD NCAICRNHIM DLCIECQANQ ASATSEECTV AWGVCNHAFH FHCISRWLK TRQVCPLDNR EWEFQKYGH UniProtKB: E3 ubiquitin-protein ligase RBX1 |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Concentration | 3 mg/mL |
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Buffer | pH: 7.5 |
Vitrification | Cryogen name: ETHANE |
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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: 60.0 e/Å2 |
Electron beam | Acceleration voltage: 200 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.8000000000000003 µm / Nominal defocus min: 0.7000000000000001 µm |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |