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Yorodumi- EMDB-35461: Protomer 1 and 2 of the asymmetry trimer of the Cul2-Rbx1-EloBC-F... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-35461 | |||||||||
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Title | Protomer 1 and 2 of the asymmetry trimer of the Cul2-Rbx1-EloBC-FEM1B ubiquitin ligase complex | |||||||||
Map data | ||||||||||
Sample |
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Keywords | Complex / E3 ubiquitin ligase / Cullin / Oligomer / LIGASE | |||||||||
Function / homology | Function and homology information regulation of ubiquitin-protein transferase activity / epithelial cell maturation involved in prostate gland development / branching involved in prostate gland morphogenesis / cullin-RING-type E3 NEDD8 transferase / cellular response to chemical stress / NEDD8 transferase activity / cullin-RING ubiquitin ligase complex / regulation of DNA damage checkpoint / Cul7-RING ubiquitin ligase complex / ubiquitin-dependent protein catabolic process via the C-end degron rule pathway ...regulation of ubiquitin-protein transferase activity / epithelial cell maturation involved in prostate gland development / branching involved in prostate gland morphogenesis / cullin-RING-type E3 NEDD8 transferase / cellular response to chemical stress / NEDD8 transferase activity / cullin-RING ubiquitin ligase complex / regulation of DNA damage checkpoint / 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 / target-directed miRNA degradation / elongin complex / VCB complex / positive regulation of protein autoubiquitination / death receptor binding / protein neddylation / regulation of extrinsic apoptotic signaling pathway via death domain receptors / negative regulation of non-canonical NF-kappaB signal transduction / 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 / 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 / Pausing and recovery of Tat-mediated HIV elongation / Tat-mediated HIV elongation arrest and recovery / cullin family protein binding / HIV elongation arrest and recovery / Pausing and recovery of HIV elongation / ubiquitin-like ligase-substrate adaptor activity / Tat-mediated elongation of the HIV-1 transcript / Formation of HIV-1 elongation complex containing HIV-1 Tat / protein K48-linked ubiquitination / Formation of HIV elongation complex in the absence of HIV Tat / Nuclear events stimulated by ALK signaling in cancer / RNA Polymerase II Transcription Elongation / Formation of RNA Pol II elongation complex / positive regulation of TORC1 signaling / RNA Polymerase II Pre-transcription Events / T cell activation / Regulation of BACH1 activity / intrinsic apoptotic signaling pathway / post-translational protein modification / transcription corepressor binding / Degradation of DVL / transcription elongation by RNA polymerase II / TP53 Regulates Transcription of DNA Repair Genes / transcription initiation at RNA polymerase II promoter / 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 / DNA Damage Recognition in GG-NER / 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 / 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 / Inactivation of CSF3 (G-CSF) signaling / 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 / 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 / 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 / ubiquitin-protein transferase activity / Regulation of RUNX2 expression and activity / cellular response to UV / KEAP1-NFE2L2 pathway / MAPK cascade / ubiquitin protein ligase activity / Antigen processing: Ubiquitination & Proteasome degradation / positive regulation of proteasomal ubiquitin-dependent protein catabolic process / protein-macromolecule adaptor activity / Neddylation Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 4.2 Å | |||||||||
Authors | Dai Z / Liang L / Yin YX | |||||||||
Funding support | China, 1 items
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Citation | Journal: EMBO J / Year: 2024 Title: Structural insights into the ubiquitylation strategy of the oligomeric CRL2 E3 ubiquitin ligase. Authors: Zonglin Dai / Ling Liang / Weize Wang / Peng Zuo / Shang Yu / Yaqi Liu / Xuyang Zhao / Yishuo Lu / Yan Jin / Fangting Zhang / Dian Ding / Weiwei Deng / Yuxin Yin / Abstract: Cullin-RING E3 ubiquitin ligase (CRL) family members play critical roles in numerous biological processes and diseases including cancer and Alzheimer's disease. Oligomerization of CRLs has been ...Cullin-RING E3 ubiquitin ligase (CRL) family members play critical roles in numerous biological processes and diseases including cancer and Alzheimer's disease. Oligomerization of CRLs has been reported to be crucial for the regulation of their activities. However, the structural basis for its regulation and mechanism of its oligomerization are not fully known. Here, we present cryo-EM structures of oligomeric CRL2 in its unneddylated state, neddylated state in complex with BEX2 as well as neddylated state in complex with FNIP1/FLCN. These structures reveal that asymmetric dimerization of N8-CRL2 is critical for the ubiquitylation of BEX2 while FNIP1/FLCN is ubiquitylated by monomeric CRL2. Our data present an example of the asymmetric homo-dimerization of CRL. Taken together, this study sheds light on the ubiquitylation strategy of oligomeric CRL2 according to substrates with different scales. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_35461.map.gz | 121.7 MB | EMDB map data format | |
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Header (meta data) | emd-35461-v30.xml emd-35461.xml | 20.4 KB 20.4 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_35461_fsc.xml | 13.4 KB | Display | FSC data file |
Images | emd_35461.png | 76.7 KB | ||
Filedesc metadata | emd-35461.cif.gz | 6.8 KB | ||
Others | emd_35461_half_map_1.map.gz emd_35461_half_map_2.map.gz | 226.8 MB 226.8 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-35461 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-35461 | HTTPS FTP |
-Validation report
Summary document | emd_35461_validation.pdf.gz | 1 MB | Display | EMDB validaton report |
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Full document | emd_35461_full_validation.pdf.gz | 1 MB | Display | |
Data in XML | emd_35461_validation.xml.gz | 22.2 KB | Display | |
Data in CIF | emd_35461_validation.cif.gz | 28.7 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-35461 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-35461 | HTTPS FTP |
-Related structure data
Related structure data | 8ij1MC 8je1C 8je2C 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_35461.map.gz / Format: CCP4 / Size: 244.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Voxel size | X=Y=Z: 0.92 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #2
File | emd_35461_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_35461_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Unneddylated Cul2-Rbx1-EloBC-FEM1B ubiquitin ligase complex
Entire | Name: Unneddylated Cul2-Rbx1-EloBC-FEM1B ubiquitin ligase complex |
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Components |
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-Supramolecule #1: Unneddylated Cul2-Rbx1-EloBC-FEM1B ubiquitin ligase complex
Supramolecule | Name: Unneddylated Cul2-Rbx1-EloBC-FEM1B ubiquitin ligase complex type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#5 |
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Source (natural) | Organism: Homo sapiens (human) |
-Macromolecule #1: Cullin-2
Macromolecule | Name: Cullin-2 / type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 87.92782 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: MSLKPRVVDF DETWNKLLTT IKAVVMLEYV ERATWNDRFS DIYALCVAYP EPLGERLYTE TKIFLENHVR HLHKRVLESE EQVLVMYHR YWEEYSKGAD YMDCLYRYLN TQFIKKNKLT EADLQYGYGG VDMNEPLMEI GELALDMWRK LMVEPLQAIL I RMLLREIK ...String: MSLKPRVVDF DETWNKLLTT IKAVVMLEYV ERATWNDRFS DIYALCVAYP EPLGERLYTE TKIFLENHVR HLHKRVLESE EQVLVMYHR YWEEYSKGAD YMDCLYRYLN TQFIKKNKLT EADLQYGYGG VDMNEPLMEI GELALDMWRK LMVEPLQAIL I RMLLREIK NDRGGEDPNQ KVIHGVINSF VHVEQYKKKF PLKFYQEIFE SPFLTETGEY YKQEASNLLQ ESNCSQYMEK VL GRLKDEE IRCRKYLHPS SYTKVIHECQ QRMVADHLQF LHAECHNIIR QEKKNDMANM YVLLRAVSTG LPHMIQELQN HIH DEGLRA TSNLTQENMP TLFVESVLEV HGKFVQLINT VLNGDQHFMS ALDKALTSVV NYREPKSVCK APELLAKYCD NLLK KSAKG MTENEVEDRL TSFITVFKYI DDKDVFQKFY ARMLAKRLIH GLSMSMDSEE AMINKLKQAC GYEFTSKLHR MYTDM SVSA DLNNKFNNFI KNQDTVIDLG ISFQIYVLQA GAWPLTQAPS STFAIPQELE KSVQMFELFY SQHFSGRKLT WLHYLC TGE VKMNYLGKPY VAMVTTYQMA VLLAFNNSET VSYKELQDST QMNEKELTKT IKSLLDVKMI NHDSEKEDID AESSFSL NM NFSSKRTKFK ITTSMQKDTP QEMEQTRSAV DEDRKMYLQA AIVRIMKARK VLRHNALIQE VISQSRARFN PSISMIKK C IEVLIDKQYI ERSQASADEY SYVAHHHHHH UniProtKB: Cullin-2 |
-Macromolecule #2: E3 ubiquitin-protein ligase RBX1
Macromolecule | Name: E3 ubiquitin-protein ligase RBX1 / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO / EC number: RING-type E3 ubiquitin transferase |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 12.289977 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: MAAAMDVDTP SGTNSGAGKK RFEVKKWNAV ALWAWDIVVD NCAICRNHIM DLCIECQANQ ASATSEECTV AWGVCNHAFH FHCISRWLK TRQVCPLDNR EWEFQKYGH UniProtKB: E3 ubiquitin-protein ligase RBX1 |
-Macromolecule #3: Elongin-B
Macromolecule | Name: Elongin-B / type: protein_or_peptide / ID: 3 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 11.748406 KDa |
Recombinant expression | Organism: Escherichia coli (E. coli) |
Sequence | String: MDVFLMIRRH KTTIFTDAKE SSTVFELKRI VEGILKRPPD EQRLYKDDQL LDDGKTLGEC GFTSQTARPQ APATVGLAFR ADDTFEALC IEPFSSPPEL PDVMK UniProtKB: Elongin-B |
-Macromolecule #4: Elongin-C
Macromolecule | Name: Elongin-C / type: protein_or_peptide / ID: 4 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 11.045694 KDa |
Recombinant expression | Organism: Escherichia coli (E. coli) |
Sequence | String: MAMYVKLISS DGHEFIVKRE HALTSGTIKA MLSGPGQFAE NETNEVNFRE IPSHVLSKVC MYFTYKVRYT NSSTEIPEFP IAPEIALEL LMAANFLDC UniProtKB: Elongin-C |
-Macromolecule #5: Protein fem-1 homolog B
Macromolecule | Name: Protein fem-1 homolog B / type: protein_or_peptide / ID: 5 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 70.688406 KDa |
Recombinant expression | Organism: Escherichia coli (E. coli) |
Sequence | String: GEFMEGLAGY VYKAASEGKV LTLAALLLNR SESDIRYLLG YVSQQGGQRS TPLIIAARNG HAKVVRLLLE HYRVQTQQTG TVRFDGYVI DGATALWCAA GAGHFEVVKL LVSHGANVNH TTVTNSTPLR AACFDGRLDI VKYLVENNAN ISIANKYDNT C LMIAAYKG ...String: GEFMEGLAGY VYKAASEGKV LTLAALLLNR SESDIRYLLG YVSQQGGQRS TPLIIAARNG HAKVVRLLLE HYRVQTQQTG TVRFDGYVI DGATALWCAA GAGHFEVVKL LVSHGANVNH TTVTNSTPLR AACFDGRLDI VKYLVENNAN ISIANKYDNT C LMIAAYKG HTDVVRYLLE QRADPNAKAH CGATALHFAA EAGHIDIVKE LIKWRAAIVV NGHGMTPLKV AAESCKADVV EL LLSHADC DRRSRIEALE LLGASFANDR ENYDIIKTYH YLYLAMLERF QDGDNILEKE VLPPIHAYGN RTECRNPQEL ESI RQDRDA LHMEGLIVRE RILGADNIDV SHPIIYRGAV YADNMEFEQC IKLWLHALHL RQKGNRNTHK DLLRFAQVFS QMIH LNETV KAPDIECVLR CSVLEIEQSM NRVKNISDAD VHNAMDNYEC NLYTFLYLVC ISTKTQCSEE DQCKINKQIY NLIHL DPRT REGFTLLHLA VNSNTPVDDF HTNDVCSFPN ALVTKLLLDC GAEVNAVDNE GNSALHIIVQ YNRPISDFLT LHSIII SLV EAGAHTDMTN KQNKTPLDKS TTGVSEILLK TQMKMSLKCL AARAVRANDI NYQDQIPRTL EEFVGFH UniProtKB: Protein fem-1 homolog B |
-Macromolecule #6: ZINC ION
Macromolecule | Name: ZINC ION / type: ligand / ID: 6 / Number of copies: 5 / 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 | 1.78 mg/mL |
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Buffer | pH: 7.5 |
Grid | Model: Quantifoil R0.6/1 / Material: GOLD / Mesh: 300 / Support film - Material: GOLD |
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) / Number grids imaged: 1 / Average electron dose: 50.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 0.01 mm / Nominal defocus max: 2.0 µm / Nominal defocus min: 1.5 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |