+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-37247 | |||||||||
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Title | CULLIN3-KLHL22-RBX1 E3 ligase | |||||||||
Map data | ||||||||||
Sample |
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Keywords | E3 ligase / STRUCTURAL PROTEIN | |||||||||
Function / homology | Function and homology information liver morphogenesis / positive regulation of mitotic cell cycle phase transition / trophectodermal cellular morphogenesis / POZ domain binding / nuclear protein quality control by the ubiquitin-proteasome system / regulation protein catabolic process at postsynapse / polar microtubule / anaphase-promoting complex-dependent catabolic process / COPII vesicle coating / cullin-RING-type E3 NEDD8 transferase ...liver morphogenesis / positive regulation of mitotic cell cycle phase transition / trophectodermal cellular morphogenesis / POZ domain binding / nuclear protein quality control by the ubiquitin-proteasome system / regulation protein catabolic process at postsynapse / polar microtubule / anaphase-promoting complex-dependent catabolic process / COPII vesicle coating / cullin-RING-type E3 NEDD8 transferase / stem cell division / cellular response to chemical stress / NEDD8 transferase activity / cellular response to L-leucine / RHOBTB3 ATPase cycle / cullin-RING ubiquitin ligase complex / embryonic cleavage / cell projection organization / positive regulation of mitotic metaphase/anaphase transition / 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 / Notch binding / NEDD8 ligase activity / RHOBTB1 GTPase cycle / Cul5-RING ubiquitin ligase complex / negative regulation of response to oxidative stress / ubiquitin-ubiquitin ligase activity / fibroblast apoptotic process / Cul4A-RING E3 ubiquitin ligase complex / SCF ubiquitin ligase complex / negative regulation of Rho protein signal transduction / Cul2-RING ubiquitin ligase complex / negative regulation of type I interferon production / Cul4B-RING E3 ubiquitin ligase complex / ubiquitin ligase complex scaffold activity / mitotic metaphase chromosome alignment / SCF-dependent proteasomal ubiquitin-dependent protein catabolic process / Cul3-RING ubiquitin ligase complex / intercellular bridge / mitotic spindle assembly checkpoint signaling / stress fiber assembly / Prolactin receptor signaling / positive regulation of cytokinesis / protein monoubiquitination / mitotic sister chromatid segregation / cullin family protein binding / ubiquitin-like ligase-substrate adaptor activity / sperm flagellum / protein autoubiquitination / RHOBTB2 GTPase cycle / protein K48-linked ubiquitination / Nuclear events stimulated by ALK signaling in cancer / endoplasmic reticulum to Golgi vesicle-mediated transport / gastrulation / 14-3-3 protein binding / positive regulation of TORC1 signaling / T cell activation / Regulation of BACH1 activity / negative regulation of autophagy / intrinsic apoptotic signaling pathway / cyclin binding / post-translational protein modification / positive regulation of protein ubiquitination / integrin-mediated signaling pathway / 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 / 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 / protein destabilization / 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 / 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 / mitotic spindle / Wnt signaling pathway / 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 / spindle pole / Interleukin-1 signaling / Orc1 removal from chromatin / Dual incision in TC-NER / G1/S transition of mitotic cell cycle Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.67 Å | |||||||||
Authors | Su M-Y | |||||||||
Funding support | China, 1 items
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Citation | Journal: Structure / Year: 2023 Title: Cryo-EM structure of the KLHL22 E3 ligase bound to an oligomeric metabolic enzyme. Authors: Fei Teng / Yang Wang / Ming Liu / Shuyun Tian / Goran Stjepanovic / Ming-Yuan Su / Abstract: CULLIN-RING ligases constitute the largest group of E3 ubiquitin ligases. While some CULLIN family members recruit adapters before engaging further with different substrate receptors, homo-dimeric ...CULLIN-RING ligases constitute the largest group of E3 ubiquitin ligases. While some CULLIN family members recruit adapters before engaging further with different substrate receptors, homo-dimeric BTB-Kelch family proteins combine adapter and substrate receptor into a single polypeptide for the CULLIN3 family. However, the entire structural assembly and molecular details have not been elucidated to date. Here, we present a cryo-EM structure of the CULLIN3 in complex with Kelch-like protein 22 (KLHL22) and a mitochondrial glutamate dehydrogenase complex I (GDH1) at 3.06 Å resolution. The structure adopts a W-shaped architecture formed by E3 ligase dimers. Three CULLIN3 dimers were found to be dynamically associated with a single GDH1 hexamer. CULLIN3 ligase mediated the polyubiquitination of GDH1 in vitro. Together, these results enabled the establishment of a structural model for understanding the complete assembly of BTB-Kelch proteins with CULLIN3 and how together they recognize oligomeric substrates and target them for ubiquitination. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_37247.map.gz | 208 MB | EMDB map data format | |
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Header (meta data) | emd-37247-v30.xml emd-37247.xml | 18.4 KB 18.4 KB | Display Display | EMDB header |
Images | emd_37247.png | 28.4 KB | ||
Filedesc metadata | emd-37247.cif.gz | 6.2 KB | ||
Others | emd_37247_additional_1.map.gz emd_37247_half_map_1.map.gz emd_37247_half_map_2.map.gz | 372 MB 392 MB 392 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-37247 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-37247 | HTTPS FTP |
-Validation report
Summary document | emd_37247_validation.pdf.gz | 778.6 KB | Display | EMDB validaton report |
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Full document | emd_37247_full_validation.pdf.gz | 778.2 KB | Display | |
Data in XML | emd_37247_validation.xml.gz | 18 KB | Display | |
Data in CIF | emd_37247_validation.cif.gz | 21.4 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-37247 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-37247 | HTTPS FTP |
-Related structure data
Related structure data | 8khpMC 8kgyC 8w4jC C: citing same article (ref.) M: atomic model generated by this map |
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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_37247.map.gz / Format: CCP4 / Size: 421.9 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Voxel size | X=Y=Z: 0.85 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Additional map: #1
File | emd_37247_additional_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_37247_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_37247_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : CULLIN3-KLHL22-RBX1 E3 ligase
Entire | Name: CULLIN3-KLHL22-RBX1 E3 ligase |
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Components |
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-Supramolecule #1: CULLIN3-KLHL22-RBX1 E3 ligase
Supramolecule | Name: CULLIN3-KLHL22-RBX1 E3 ligase / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: Homo sapiens (human) |
-Macromolecule #1: Kelch-like protein 22
Macromolecule | Name: Kelch-like protein 22 / 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: 71.744594 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MAEEQEFTQL CKLPAQPSHP HCVNNTYRSA QHSQALLRGL LALRDSGILF DVVLVVEGRH IEAHRILLAA SCDYFRGMFA GGLKEMEQE EVLIHGVSYN AMCQILHFIY TSELELSLSN VQETLVAACQ LQIPEIIHFC CDFLMSWVDE ENILDVYRLA E LFDLSRLT ...String: MAEEQEFTQL CKLPAQPSHP HCVNNTYRSA QHSQALLRGL LALRDSGILF DVVLVVEGRH IEAHRILLAA SCDYFRGMFA GGLKEMEQE EVLIHGVSYN AMCQILHFIY TSELELSLSN VQETLVAACQ LQIPEIIHFC CDFLMSWVDE ENILDVYRLA E LFDLSRLT EQLDTYILKN FVAFSRTDKY RQLPLEKVYS LLSSNRLEVS CETEVYEGAL LYHYSLEQVQ ADQISLHEPP KL LETVRFP LMEAEVLQRL HDKLDPSPLR DTVASALMYH RNESLQPSLQ SPQTELRSDF QCVVGFGGIH STPSTVLSDQ AKY LNPLLG EWKHFTASLA PRMSNQGIAV LNNFVYLIGG DNNVQGFRAE SRCWRYDPRH NRWFQIQSLQ QEHADLSVCV VGRY IYAVA GRDYHNDLNA VERYDPATNS WAYVAPLKRE VYAHAGATLE GKMYITCGRR GEDYLKETHC YDPGSNTWHT LADGP VRRA WHGMATLLNK LYVIGGSNND AGYRRDVHQV ACYSCTSGQW SSVCPLPAGH GEPGIAVLDN RIYVLGGRSH NRGSRT GYV HIYDVEKDCW EEGPQLDNSI SGLAACVLTL PRSLLLEPPR GTPDRSQADP DFASEVMSVS DWEEFDNSSE D UniProtKB: Kelch-like protein 22 |
-Macromolecule #2: Cullin-3
Macromolecule | Name: Cullin-3 / type: protein_or_peptide / ID: 2 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 89.063328 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MSNLSKGTGS RKDTKMRIRA FPMTMDEKYV NSIWDLLKNA IQEIQRKNNS GLSFEELYRN AYTMVLHKHG EKLYTGLREV VTEHLINKV REDVLNSLNN NFLQTLNQAW NDHQTAMVMI RDILMYMDRV YVQQNNVENV YNLGLIIFRD QVVRYGCIRD H LRQTLLDM ...String: MSNLSKGTGS RKDTKMRIRA FPMTMDEKYV NSIWDLLKNA IQEIQRKNNS GLSFEELYRN AYTMVLHKHG EKLYTGLREV VTEHLINKV REDVLNSLNN NFLQTLNQAW NDHQTAMVMI RDILMYMDRV YVQQNNVENV YNLGLIIFRD QVVRYGCIRD H LRQTLLDM IARERKGEVV DRGAIRNACQ MLMILGLEGR SVYEEDFEAP FLEMSAEFFQ MESQKFLAEN SASVYIKKVE AR INEEIER VMHCLDKSTE EPIVKVVERE LISKHMKTIV EMENSGLVHM LKNGKTEDLG CMYKLFSRVP NGLKTMCECM SSY LREQGK ALVSEEGEGK NPVDYIQGLL DLKSRFDRFL LESFNNDRLF KQTIAGDFEY FLNLNSRSPE YLSLFIDDKL KKGV KGLTE QEVETILDKA MVLFRFMQEK DVFERYYKQH LARRLLTNKS VSDDSEKNMI SKLKTECGCQ FTSKLEGMFR DMSIS NTTM DEFRQHLQAT GVSLGGVDLT VRVLTTGYWP TQSATPKCNI PPAPRHAFEI FRRFYLAKHS GRQLTLQHHM GSADLN ATF YGPVKKEDGS EVGVGGAQVT GSNTRKHILQ VSTFQMTILM LFNNREKYTF EEIQQETDIP ERELVRALQS LACGKPT QR VLTKEPKSKE IENGHIFTVN DQFTSKLHRV KIQTVAAKQG ESDPERKETR QKVDDDRKHE IEAAIVRIMK SRKKMQHN V LVAEVTQQLK ARFLPSPVVI KKRIEGLIER EYLARTPEDR KVYTYVA UniProtKB: Cullin-3 |
-Macromolecule #3: E3 ubiquitin-protein ligase RBX1
Macromolecule | Name: E3 ubiquitin-protein ligase RBX1 / type: protein_or_peptide / ID: 3 / Number of copies: 2 / 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: Homo sapiens (human) |
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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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.4 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 1.07 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: SPOT SCAN / Imaging mode: BRIGHT FIELD / Nominal defocus max: 1.9000000000000001 µm / Nominal defocus min: 1.1 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Startup model | Type of model: INSILICO MODEL |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.67 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 181834 |
Initial angle assignment | Type: OTHER |
Final angle assignment | Type: OTHER |