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Open data
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Basic information
Entry | ![]() | |||||||||
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Title | Cryo-EM Structure of the KBTBD2-CUL3-Rbx1 dimeric complex | |||||||||
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Function / homology | ![]() 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 / ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() Similarity search - Function | |||||||||
Biological species | ![]() ![]() | |||||||||
Method | ![]() ![]() | |||||||||
![]() | Sun L / Chen Z / Hu Y / Mao Q | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Dynamic molecular architecture and substrate recruitment of cullin3-RING E3 ligase CRL3. Authors: Yuxia Hu / Zhao Zhang / Qiyu Mao / Xiang Zhang / Aihua Hao / Yu Xun / Yeda Wang / Lin Han / Wuqiang Zhan / Qianying Liu / Yue Yin / Chao Peng / Eva Marie Y Moresco / Zhenguo Chen / Bruce Beutler / Lei Sun / ![]() ![]() Abstract: Phosphatidylinositol 3-kinase α, a heterodimer of catalytic p110α and one of five regulatory subunits, mediates insulin- and insulin like growth factor-signaling and, frequently, oncogenesis. ...Phosphatidylinositol 3-kinase α, a heterodimer of catalytic p110α and one of five regulatory subunits, mediates insulin- and insulin like growth factor-signaling and, frequently, oncogenesis. Cellular levels of the regulatory p85α subunit are tightly controlled by regulated proteasomal degradation. In adipose tissue and growth plates, failure of K48-linked p85α ubiquitination causes diabetes, lipodystrophy and dwarfism in mice, as in humans with SHORT syndrome. Here we elucidated the structures of the key ubiquitin ligase complexes regulating p85α availability. Specificity is provided by the substrate receptor KBTBD2, which recruits p85α to the cullin3-RING E3 ubiquitin ligase (CRL3). CRL3 forms multimers, which disassemble into dimers upon substrate binding (CRL3-p85α) and/or neddylation by the activator NEDD8 (CRL3~N8), leading to p85α ubiquitination and degradation. Deactivation involves dissociation of NEDD8 mediated by the COP9 signalosome and displacement of KBTBD2 by the inhibitor CAND1. The hereby identified structural basis of p85α regulation opens the way to better understanding disturbances of glucose regulation, growth and cancer. | |||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 192.4 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 18.3 KB 18.3 KB | Display Display | ![]() |
Images | ![]() | 77 KB | ||
Filedesc metadata | ![]() | 6.5 KB | ||
Others | ![]() ![]() | 171.1 MB 171.1 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8gq6MC ![]() 8h33C ![]() 8h34C ![]() 8h35C ![]() 8h36C ![]() 8h37C ![]() 8h38C ![]() 8h3aC ![]() 8h3fC ![]() 8h3qC ![]() 8h3rC M: atomic model generated by this map C: citing same article ( |
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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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Voxel size | X=Y=Z: 1.332 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #2
File | emd_34199_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_34199_half_map_2.map | ||||||||||||
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Density Histograms |
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Sample components
-Entire : KBTBD2-CUL3-Rbx1 dimeric complex
Entire | Name: KBTBD2-CUL3-Rbx1 dimeric complex |
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Components |
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-Supramolecule #1: KBTBD2-CUL3-Rbx1 dimeric complex
Supramolecule | Name: KBTBD2-CUL3-Rbx1 dimeric complex / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#3 |
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Source (natural) | Organism: ![]() ![]() |
-Macromolecule #1: Kelch repeat and BTB domain-containing protein 2
Macromolecule | Name: Kelch repeat and BTB domain-containing protein 2 / type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 71.403367 KDa |
Recombinant expression | Organism: ![]() ![]() ![]() |
Sequence | String: MSTQDERQIN TEYAVSLLEQ LKLFYEQQLF TDIVLIVEGT EFPCHKMVLA TCSSYFRAMF MSGLSESKQT HVHLRNVDAA TLQIIITYA YTGNLAMNDS TVEQLYETAC FLQVEDVLQR CREYLIKKIN AENCVRLLSF ADLFSCEELK QSAKRMVEHK F TAVYHQDA ...String: MSTQDERQIN TEYAVSLLEQ LKLFYEQQLF TDIVLIVEGT EFPCHKMVLA TCSSYFRAMF MSGLSESKQT HVHLRNVDAA TLQIIITYA YTGNLAMNDS TVEQLYETAC FLQVEDVLQR CREYLIKKIN AENCVRLLSF ADLFSCEELK QSAKRMVEHK F TAVYHQDA FMQLSHDLLI DILSSDNLNV EKEETVREAA MLWLEYNTES RSQYLSSVLS QIRIDALSEV TQRAWFQGLP PN DKSVVVQ GLYKSMPKFF KPRLGMTKEE MMIFIEASSE NPCSLYSSVC YSPQAEKVYK LCSPPADLHK VGTVVTPDND IYI AGGQVP LKNTKTNHSK TSKLQTAFRT VNCFYWFDAQ QNTWFPKTPM LFVRIKPSLV CCEGYIYAIG GDSVGGELNR RTVE RYDTE KDEWTMVSPL PCAWQWSAAV VVHDCIYVMT LNLMYCYFPR SDSWVEMAMR QTSRSFASAA AFGDKIFYIG GLHIA TNSG IRLPSGTVDG SSVTVEIYDV NKNEWKMAAN IPAKRYSDPC VRAVVISNSL CVFMRETHLN ERAKYVTYQY DLELDR WSL RQHISERVLW DLGRDFRCTV GKLYPSCLEE SPWKPPTYLF STDGTEEFEL DGEMVALPPV UniProtKB: Kelch repeat and BTB domain-containing protein 2 |
-Macromolecule #2: E3 ubiquitin-protein ligase RBX1
Macromolecule | Name: E3 ubiquitin-protein ligase RBX1 / type: protein_or_peptide / ID: 2 / Number of copies: 2 / Enantiomer: LEVO / EC number: RING-type E3 ubiquitin transferase |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 13.970756 KDa |
Recombinant expression | Organism: ![]() ![]() ![]() |
Sequence | String: HHHHHHENLY FQGMAAAMDV DTPSGTNSGA GKKRFEVKKW NAVALWAWDI VVDNCAICRN HIMDLCIECQ ANQASATSEE CTVAWGVCN HAFHFHCISR WLKTRQVCPL DNREWEFQKY GH UniProtKB: E3 ubiquitin-protein ligase RBX1 |
-Macromolecule #3: Cullin-3
Macromolecule | Name: Cullin-3 / type: protein_or_peptide / ID: 3 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 90.105469 KDa |
Recombinant expression | Organism: ![]() ![]() ![]() |
Sequence | String: WSHPQFEKMS NLSKGTGSRK DTKMRIRAFP MTMDEKYVNS IWDLLKNAIQ EIQRKNNSGL SFEELYRNAY TMVLHKHGEK LYTGLREVV TEHLINKVRE DVLNSLNNNF LQTLNQAWND HQTAMVMIRD ILMYMDRVYV QQNNVENVYN LGLIIFRDQV V RYGCIRDH ...String: WSHPQFEKMS NLSKGTGSRK DTKMRIRAFP MTMDEKYVNS IWDLLKNAIQ EIQRKNNSGL SFEELYRNAY TMVLHKHGEK LYTGLREVV TEHLINKVRE DVLNSLNNNF LQTLNQAWND HQTAMVMIRD ILMYMDRVYV QQNNVENVYN LGLIIFRDQV V RYGCIRDH LRQTLLDMIA RERKGEVVDR GAIRNACQML MILGLEGRSV YEEDFEAPFL EMSAEFFQME SQKFLAENSA SV YIKKVEA RINEEIERVM HCLDKSTEEP IVKVVERELI SKHMKTIVEM ENSGLVHMLK NGKTEDLGCM YKLFSRVPNG LKT MCECMS SYLREQGKAL VSEEGEGKNP VDYIQGLLDL KSRFDRFLLE SFNNDRLFKQ TIAGDFEYFL NLNSRSPEYL SLFI DDKLK KGVKGLTEQE VETILDKAMV LFRFMQEKDV FERYYKQHLA RRLLTNKSVS DDSEKNMISK LKTECGCQFT SKLEG MFRD MSISNTTMDE FRQHLQATGV SLGGVDLTVR VLTTGYWPTQ SATPKCNIPP APRHAFEIFR RFYLAKHSGR QLTLQH HMG SADLNATFYG PVKKEDGSEV GVGGAQVTGS NTRKHILQVS TFQMTILMLF NNREKYTFEE IQQETDIPER ELVRALQ SL ACGKPTQRVL TKEPKSKEIE NGHIFTVNDQ FTSKLHRVKI QTVAAKQGES DPERKETRQK VDDDRKHEIE AAIVRIMK S RKKMQHNVLV AEVTQQLKAR FLPSPVVIKK RIEGLIEREY LARTPEDRKV YTYVA UniProtKB: ![]() |
-Macromolecule #4: ZINC ION
Macromolecule | Name: ZINC ION / type: ligand / ID: 4 / Number of copies: 6 / Formula: ZN |
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Molecular weight | Theoretical: 65.409 Da |
-Experimental details
-Structure determination
Method | ![]() |
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Aggregation state | particle |
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Sample preparation
Buffer | pH: 7.8 |
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Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD![]() |
Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: SUPER-RESOLUTION / Average electron dose: 45.0 e/Å2 |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
Startup model | Type of model: PDB ENTRY PDB model - PDB ID: Details: 4A0K |
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Initial angle assignment | Type: PROJECTION MATCHING |
Final angle assignment | Type: PROJECTION MATCHING / Software - Name: RELION (ver. 3.0) |
Final reconstruction | Applied symmetry - Point group: C1 (asymmetric) / Resolution.type: BY AUTHOR / Resolution: 3.96 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: RELION (ver. 3.0) / Number images used: 433329 |