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Yorodumi- PDB-8u80: KCTD5/Cullin3/Gbeta1gamma2 Complex: Local Refinment of KCTD5(BTB)... -
+Open data
-Basic information
Entry | Database: PDB / ID: 8u80 | ||||||
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Title | KCTD5/Cullin3/Gbeta1gamma2 Complex: Local Refinment of KCTD5(BTB)/Cullin3(NTD) | ||||||
Components |
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Keywords | LIGASE / cullin family protein / proteasome-mediated ubiquitin-dependent protein catabolic process / complex / ubiquitin-dependent protein catabolic process | ||||||
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 / negative regulation of type I interferon production / ubiquitin ligase complex scaffold activity / mitotic metaphase chromosome alignment / Cul3-RING ubiquitin ligase complex / stress fiber assembly / positive regulation of cytokinesis / protein monoubiquitination / cullin family protein binding / sperm flagellum / protein autoubiquitination / RHOBTB2 GTPase cycle / protein K48-linked ubiquitination / endoplasmic reticulum to Golgi vesicle-mediated transport / gastrulation / positive regulation of TORC1 signaling / intrinsic apoptotic signaling pathway / cyclin binding / positive regulation of protein ubiquitination / integrin-mediated signaling pathway / Degradation of DVL / cellular response to amino acid stimulus / Hedgehog 'on' state / protein destabilization / protein homooligomerization / mitotic spindle / Wnt signaling pathway / spindle pole / G1/S transition of mitotic cell cycle / Regulation of RAS by GAPs / protein polyubiquitination / KEAP1-NFE2L2 pathway / ubiquitin protein ligase activity / Antigen processing: Ubiquitination & Proteasome degradation / cell migration / Neddylation / gene expression / ubiquitin-dependent protein catabolic process / postsynapse / proteasome-mediated ubiquitin-dependent protein catabolic process / Potential therapeutics for SARS / protein ubiquitination / inflammatory response / centrosome / glutamatergic synapse / ubiquitin protein ligase binding / positive regulation of cell population proliferation / protein-containing complex binding / Golgi apparatus / negative regulation of transcription by RNA polymerase II / extracellular exosome / nucleoplasm / identical protein binding / membrane / nucleus / plasma membrane / cytoplasm / cytosol Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.6 Å | ||||||
Authors | Kuntz, D.A. / Nguyen, D.M. / Narayanan, N. / Prive, G.G. | ||||||
Funding support | Canada, 1items
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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: Proc.Natl.Acad.Sci.USA / Year: 2024 Title: Structure and dynamics of a pentameric KCTD5/Cullin3/G beta gamma E3 ubiquitin ligase complex Authors: Nguyen, D.M. / Rath, D.H. / Devost, D. / Petrin, D. / Rizk, R. / Ji, A.X. / Narayanan, N. / Yong, D. / Zhai, A. / Kuntz, D.A. / Mian, M.U.Q. / Pomroy, N.C. / Keszei, A.F.E. / Benlekbir, S. / ...Authors: Nguyen, D.M. / Rath, D.H. / Devost, D. / Petrin, D. / Rizk, R. / Ji, A.X. / Narayanan, N. / Yong, D. / Zhai, A. / Kuntz, D.A. / Mian, M.U.Q. / Pomroy, N.C. / Keszei, A.F.E. / Benlekbir, S. / Mazhab-Jafari, M.T. / Rubinstein, J.L. / Hebert, T.E. / Prive, G.G. #2: Journal: Biorxiv / Year: 2023 Title: Structure and dynamics of a pentameric KCTD5/Cullin3/G beta gamma E3 ubiquitin ligase complex Authors: Nguyen, D.M. / Rath, D.H. / Devost, D. / Petrin, D. / Rizk, R. / Ji, A.X. / Narayanan, N. / Yong, D. / Zhai, A. / Kuntz, D.A. / Mian, M.U.Q. / Pomroy, N.C. / Keszei, A.F.E. / Benlekbir, S. / ...Authors: Nguyen, D.M. / Rath, D.H. / Devost, D. / Petrin, D. / Rizk, R. / Ji, A.X. / Narayanan, N. / Yong, D. / Zhai, A. / Kuntz, D.A. / Mian, M.U.Q. / Pomroy, N.C. / Keszei, A.F.E. / Benlekbir, S. / Mazhab-Jafari, M.T. / Rubinstein, J.L. / Hebert, T.E. / Prive, G.G. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8u80.cif.gz | 945.2 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8u80.ent.gz | Display | PDB format | |
PDBx/mmJSON format | 8u80.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8u80_validation.pdf.gz | 1.1 MB | Display | wwPDB validaton report |
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Full document | 8u80_full_validation.pdf.gz | 1.1 MB | Display | |
Data in XML | 8u80_validation.xml.gz | 77.6 KB | Display | |
Data in CIF | 8u80_validation.cif.gz | 115.7 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/u8/8u80 ftp://data.pdbj.org/pub/pdb/validation_reports/u8/8u80 | HTTPS FTP |
-Related structure data
Related structure data | 41995MC 8u7zC 8u81C 8u82C 8u83C 8u84C M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
Experimental dataset #1 | Data reference: 10.5281/zenodo.8341597 / Data set type: other data / Details: Zenodo |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
#1: Protein | Mass: 26125.562 Da / Num. of mol.: 5 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: KCTD5 / Production host: Escherichia coli BL21(DE3) (bacteria) / References: UniProt: Q9NXV2 #2: Protein | Mass: 44535.152 Da / Num. of mol.: 5 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: CUL3, KIAA0617 / Production host: Escherichia coli BL21(DE3) (bacteria) / References: UniProt: Q13618 |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: Complex of substrate adaptor KCTD5 with Cullin-3 and substrate Gbeta-gamma Type: COMPLEX / Entity ID: all / Source: RECOMBINANT |
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Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Escherichia coli BL21(DE3) (bacteria) |
Buffer solution | pH: 7.5 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 1500 nm / Nominal defocus min: 250 nm |
Image recording | Electron dose: 49.35 e/Å2 / Film or detector model: FEI FALCON IV (4k x 4k) / Num. of real images: 7464 |
-Processing
EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
Symmetry | Point symmetry: C1 (asymmetric) | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.6 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 64612 / Symmetry type: POINT | ||||||||||||||||||||||||
Refinement | Cross valid method: NONE Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2 | ||||||||||||||||||||||||
Displacement parameters | Biso mean: 172.2 Å2 | ||||||||||||||||||||||||
Refine LS restraints |
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