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Yorodumi- EMDB-42008: KCTD5/Cullin3/Gbeta1gamma2 Complex State D: Composite Map from RE... -
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-Basic information
Entry | Database: EMDB / ID: EMD-42008 | |||||||||
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Title | KCTD5/Cullin3/Gbeta1gamma2 Complex State D: Composite Map from RELION Multi-body Refinement | |||||||||
Map data | KCTD5:Cullin3:GBetaGamma StateD Composite map from Multibody::Full Map | |||||||||
Sample |
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Keywords | cullin family protein / proteasome-mediated ubiquitin-dependent protein catabolic process / complex / ubiquitin-dependent protein catabolic process / CYTOSOLIC 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 / stem cell division ...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 / stem cell division / RHOBTB3 ATPase cycle / embryonic cleavage / cell projection organization / positive regulation of mitotic metaphase/anaphase transition / Notch binding / RHOBTB1 GTPase cycle / fibroblast apoptotic process / negative regulation of Rho protein signal transduction / ubiquitin ligase complex scaffold activity / negative regulation of type I interferon production / mitotic metaphase chromosome alignment / Cul3-RING ubiquitin ligase complex / stress fiber assembly / protein monoubiquitination / positive regulation of cytokinesis / cullin family protein binding / cyclin binding / sperm flagellum / protein K48-linked ubiquitination / RHOBTB2 GTPase cycle / protein autoubiquitination / endoplasmic reticulum to Golgi vesicle-mediated transport / regulation of cellular response to insulin stimulus / gastrulation / positive regulation of TORC1 signaling / intrinsic apoptotic signaling pathway / cellular response to amino acid stimulus / positive regulation of protein ubiquitination / integrin-mediated signaling pathway / Degradation of DVL / Hedgehog 'on' state / protein destabilization / Olfactory Signaling Pathway / Activation of the phototransduction cascade / protein homooligomerization / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / G protein-coupled acetylcholine receptor signaling pathway / G-protein activation / G1/S transition of mitotic cell cycle / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / Prostacyclin signalling through prostacyclin receptor / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / mitotic spindle / Wnt signaling pathway / ADP signalling through P2Y purinoceptor 12 / G beta:gamma signalling through BTK / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / Sensory perception of sweet, bitter, and umami (glutamate) taste / photoreceptor disc membrane / spindle pole / Adrenaline,noradrenaline inhibits insulin secretion / Glucagon-type ligand receptors / Vasopressin regulates renal water homeostasis via Aquaporins / G alpha (z) signalling events / cellular response to catecholamine stimulus / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / ADORA2B mediated anti-inflammatory cytokines production / sensory perception of taste / Regulation of RAS by GAPs / protein polyubiquitination / ADP signalling through P2Y purinoceptor 1 / adenylate cyclase-activating dopamine receptor signaling pathway / G beta:gamma signalling through PI3Kgamma / cellular response to prostaglandin E stimulus / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / GPER1 signaling / G-protein beta-subunit binding / Inactivation, recovery and regulation of the phototransduction cascade / heterotrimeric G-protein complex / ubiquitin protein ligase activity / KEAP1-NFE2L2 pathway / G alpha (12/13) signalling events / extracellular vesicle / Antigen processing: Ubiquitination & Proteasome degradation / signaling receptor complex adaptor activity / cell migration / Thrombin signalling through proteinase activated receptors (PARs) / GTPase binding / retina development in camera-type eye / Ca2+ pathway / Neddylation / phospholipase C-activating G protein-coupled receptor signaling pathway / gene expression / G alpha (i) signalling events / fibroblast proliferation / ubiquitin-dependent protein catabolic process Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.88 Å | |||||||||
Authors | Nguyen DM / Narayanan N / Kuntz DA / Prive GG | |||||||||
Funding support | Canada, 1 items
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Citation | Journal: Proc Natl Acad Sci U S A / Year: 2024 Title: Structure and dynamics of a pentameric KCTD5/CUL3/Gβγ E3 ubiquitin ligase complex. Authors: Duc Minh Nguyen / Deanna H Rath / Dominic Devost / Darlaine Pétrin / Robert Rizk / Alan X Ji / Naveen Narayanan / Darren Yong / Andrew Zhai / Douglas A Kuntz / Maha U Q Mian / Neil C Pomroy ...Authors: Duc Minh Nguyen / Deanna H Rath / Dominic Devost / Darlaine Pétrin / Robert Rizk / Alan X Ji / Naveen Narayanan / Darren Yong / Andrew Zhai / Douglas A Kuntz / Maha U Q Mian / Neil C Pomroy / Alexander F A Keszei / Samir Benlekbir / Mohammad T Mazhab-Jafari / John L Rubinstein / Terence E Hébert / Gilbert G Privé / Abstract: Heterotrimeric G proteins can be regulated by posttranslational modifications, including ubiquitylation. KCTD5, a pentameric substrate receptor protein consisting of an N-terminal BTB domain and a C- ...Heterotrimeric G proteins can be regulated by posttranslational modifications, including ubiquitylation. KCTD5, a pentameric substrate receptor protein consisting of an N-terminal BTB domain and a C-terminal domain, engages CUL3 to form the central scaffold of a cullin-RING E3 ligase complex (CRL3) that ubiquitylates Gβγ and reduces Gβγ protein levels in cells. The cryo-EM structure of a 5:5:5 KCTD5/CUL3/Gβγ assembly reveals a highly dynamic complex with rotations of over 60° between the KCTD5/CUL3 and KCTD5/Gβγ moieties of the structure. CRL3 engages the E3 ligase ARIH1 to ubiquitylate Gβγ in an E3-E3 superassembly, and extension of the structure to include full-length CUL3 with RBX1 and an ARIH1~ubiquitin conjugate reveals that some conformational states position the ARIH1~ubiquitin thioester bond to within 10 Å of lysine-23 of Gβ and likely represent priming complexes. Most previously described CRL/substrate structures have consisted of monovalent complexes and have involved flexible peptide substrates. The structure of the KCTD5/CUL3/Gβγ complex shows that the oligomerization of a substrate receptor can generate a polyvalent E3 ligase complex and that the internal dynamics of the substrate receptor can position a structured target for ubiquitylation in a CRL3 complex. #1: Journal: Biorxiv / Year: 2023 Title: Structure and dynamics of a pentameric KCTD5/Cullin3/G beta gamma E3 ubiquitin ligase complex Authors: Nguyen DM / Rath DH / Devost D / Petrin D / Rizk R / Ji AX / Narayanan N / Yong D / Zhai A / Kuntz DA / Mian MUQ / Pomroy NC / Keszei AFE / Benlekbir S / Mazhab-Jafari MT / Rubinstein JL / Hebert TE / Prive GG | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_42008.map.gz | 109.2 MB | EMDB map data format | |
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Header (meta data) | emd-42008-v30.xml emd-42008.xml | 20.7 KB 20.7 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_42008_fsc.xml | 11.6 KB | Display | FSC data file |
Images | emd_42008.png | 109.8 KB | ||
Masks | emd_42008_msk_1.map | 129.7 MB | Mask map | |
Filedesc metadata | emd-42008.cif.gz | 6.2 KB | ||
Others | emd_42008_half_map_1.map.gz emd_42008_half_map_2.map.gz | 109.5 MB 109.5 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-42008 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-42008 | HTTPS FTP |
-Validation report
Summary document | emd_42008_validation.pdf.gz | 793.3 KB | Display | EMDB validaton report |
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Full document | emd_42008_full_validation.pdf.gz | 792.9 KB | Display | |
Data in XML | emd_42008_validation.xml.gz | 19.1 KB | Display | |
Data in CIF | emd_42008_validation.cif.gz | 24 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-42008 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-42008 | HTTPS FTP |
-Related structure data
Related structure data | 8u84MC 8u7zC 8u80C 8u81C 8u82C 8u83C 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_42008.map.gz / Format: CCP4 / Size: 129.7 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Annotation | KCTD5:Cullin3:GBetaGamma StateD Composite map from Multibody::Full Map | ||||||||||||||||||||
Voxel size | X=Y=Z: 1.03 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Mask #1
File | emd_42008_msk_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: KCTD5:Cullin3:GBetaGamma StateD Composite map from Multibody:: Half Map...
File | emd_42008_half_map_1.map | ||||||||||||
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Annotation | KCTD5:Cullin3:GBetaGamma StateD Composite map from Multibody:: Half Map 1 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: KCTD5:Cullin3:GBetaGamma StateD Composite map from Multibody:: Half Map...
File | emd_42008_half_map_2.map | ||||||||||||
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Annotation | KCTD5:Cullin3:GBetaGamma StateD Composite map from Multibody:: Half Map 1 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Complex of substrate adaptor KCTD5 with Cullin-3 and substrate Gb...
Entire | Name: Complex of substrate adaptor KCTD5 with Cullin-3 and substrate Gbeta-gamma |
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Components |
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-Supramolecule #1: Complex of substrate adaptor KCTD5 with Cullin-3 and substrate Gb...
Supramolecule | Name: Complex of substrate adaptor KCTD5 with Cullin-3 and substrate Gbeta-gamma type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: Homo sapiens (human) |
-Macromolecule #1: KCTD5_HUMAN
Macromolecule | Name: KCTD5_HUMAN / type: protein_or_peptide / ID: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Sequence | String: MAENHCELLS PARGGIGAGL GGGLCRRCSA GLGALAQRPG SVSKWVRLNV GGTYFLTTRQ TLCRDPKSF LYRLCQADPD LDSDKDETGA YLIDRDPTYF GPVLNYLRHG KLVINKDLAE E GVLEEAEF YNITSLIKLV KDKIRERDSK TSQVPVKHVY RVLQCQEEEL ...String: MAENHCELLS PARGGIGAGL GGGLCRRCSA GLGALAQRPG SVSKWVRLNV GGTYFLTTRQ TLCRDPKSF LYRLCQADPD LDSDKDETGA YLIDRDPTYF GPVLNYLRHG KLVINKDLAE E GVLEEAEF YNITSLIKLV KDKIRERDSK TSQVPVKHVY RVLQCQEEEL TQMVSTMSDG WK FEQLVSI GSSYNYGNED QAEFLCVVSK ELHNTPYGTA SEPSEKAKIL QERGSRM UniProtKB: BTB/POZ domain-containing protein KCTD5 |
-Macromolecule #2: cullin3 1-381
Macromolecule | Name: cullin3 1-381 / type: protein_or_peptide / ID: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Sequence | String: MSNLSKGTGS RKDTKMRIRA FPMTMDEKYV NSIWDLLKNA IQEIQRKNNS GLSFEELYRN AYTMVLHKHG EKLYTGLREV VTEHLINKVR EDVLNSLNNN FLQTLNQAWN DHQTAMVMIR DILMYMDRVY VQQNNVENVY NLGLIIFRDQ VVRYGCIRDH LRQTLLDMIA ...String: MSNLSKGTGS RKDTKMRIRA FPMTMDEKYV NSIWDLLKNA IQEIQRKNNS GLSFEELYRN AYTMVLHKHG EKLYTGLREV VTEHLINKVR EDVLNSLNNN FLQTLNQAWN DHQTAMVMIR DILMYMDRVY VQQNNVENVY NLGLIIFRDQ VVRYGCIRDH LRQTLLDMIA RERKGEVVDR GAIRNACQML MILGLEGRSV YEEDFEAPFL EMSAEFFQME SQKFLAENSA SVYIKKVEAR INEEIERVMH CLDKSTEEPI VKVVERELIS KHMKTIVEME NSGLVHMLKN GKTEDLGCMY KLFSRVPNGL KTMCECMSSY LREQGKALVS EEGEGKNPVD YIQGLLDLKS RFDRFLLESF NNDRLFKQTI AGDFEYFLNL N UniProtKB: Cullin-3 |
-Macromolecule #3: GBB1_HUMAN
Macromolecule | Name: GBB1_HUMAN / type: protein_or_peptide / ID: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MSELDQLRQE AEQLKNQIRD ARKACADATL SQITNNIDPV GRIQMRTRRT LRGHLAKIYA MHWGTDSRL LVSASQDGKL IIWDSYTTNK VHAIPLRSSW VMTCAYAPSG NYVACGGLDN I CSIYNLKT REGNVRVSRE LAGHTGYLSC CRFLDDNQIV TSSGDTTCAL ...String: MSELDQLRQE AEQLKNQIRD ARKACADATL SQITNNIDPV GRIQMRTRRT LRGHLAKIYA MHWGTDSRL LVSASQDGKL IIWDSYTTNK VHAIPLRSSW VMTCAYAPSG NYVACGGLDN I CSIYNLKT REGNVRVSRE LAGHTGYLSC CRFLDDNQIV TSSGDTTCAL WDIETGQQTT TF TGHTGDV MSLSLAPDTR LFVSGACDAS AKLWDVREGM CRQTFTGHES DINAICFFPN GNA FATGSD DATCRLFDLR ADQELMTYSH DNIICGITSV SFSKSGRLLL AGYDDFNCNV WDAL KADRA GVLAGHDNRV SCLGVTDDGM AVATGSWDSF LKIWN UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 |
-Macromolecule #4: GBG2_HUMAN
Macromolecule | Name: GBG2_HUMAN / type: protein_or_peptide / ID: 4 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MASNNTASIA QARKLVEQLK MEANIDRIKV SKAAADLMAY CEAHAKEDPL LTPVPASENP FREKKFFSA IL UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.5 |
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Vitrification | Cryogen name: ETHANE / Instrument: FEI VITROBOT MARK IV |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: FEI FALCON IV (4k x 4k) / Number real images: 7464 / Average electron dose: 49.35 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 1.5 µm / Nominal defocus min: 0.25 µm / Nominal magnification: 75000 |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
+Image processing
-Atomic model buiding 1
Refinement | Space: REAL / Protocol: FLEXIBLE FIT |
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Output model | PDB-8u84: |