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- EMDB-27201: EM map of the human UBR5 HECT-type E3 ubiquitin ligase in a dimer... -
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Open data
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Basic information
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Title | EM map of the human UBR5 HECT-type E3 ubiquitin ligase in a dimeric form | |||||||||
![]() | Primary map | |||||||||
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![]() | HECT / E3 ligase / Dimer / LIGASE | |||||||||
Function / homology | ![]() cytoplasm protein quality control / heterochromatin boundary formation / cytoplasm protein quality control by the ubiquitin-proteasome system / protein K29-linked ubiquitination / nuclear protein quality control by the ubiquitin-proteasome system / HECT-type E3 ubiquitin transferase / protein K11-linked ubiquitination / DNA repair-dependent chromatin remodeling / ubiquitin-ubiquitin ligase activity / progesterone receptor signaling pathway ...cytoplasm protein quality control / heterochromatin boundary formation / cytoplasm protein quality control by the ubiquitin-proteasome system / protein K29-linked ubiquitination / nuclear protein quality control by the ubiquitin-proteasome system / HECT-type E3 ubiquitin transferase / protein K11-linked ubiquitination / DNA repair-dependent chromatin remodeling / ubiquitin-ubiquitin ligase activity / progesterone receptor signaling pathway / protein K48-linked ubiquitination / negative regulation of smoothened signaling pathway / ubiquitin binding / positive regulation of protein import into nucleus / protein polyubiquitination / positive regulation of canonical Wnt signaling pathway / ubiquitin protein ligase activity / proteasome-mediated ubiquitin-dependent protein catabolic process / DNA repair / DNA damage response / positive regulation of gene expression / chromatin / perinuclear region of cytoplasm / protein-containing complex / RNA binding / zinc ion binding / nucleoplasm / membrane / nucleus / cytoplasm / cytosol Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.8 Å | |||||||||
![]() | Wang F / He Q / Lin G / Li H | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Structure of the human UBR5 E3 ubiquitin ligase. Authors: Feng Wang / Qing He / Wenhu Zhan / Ziqi Yu / Efrat Finkin-Groner / Xiaojing Ma / Gang Lin / Huilin Li / ![]() Abstract: The human UBR5 is a single polypeptide chain homology to E6AP C terminus (HECT)-type E3 ubiquitin ligase essential for embryonic development in mammals. Dysregulated UBR5 functions like an ...The human UBR5 is a single polypeptide chain homology to E6AP C terminus (HECT)-type E3 ubiquitin ligase essential for embryonic development in mammals. Dysregulated UBR5 functions like an oncoprotein to promote cancer growth and metastasis. Here, we report that UBR5 assembles into a dimer and a tetramer. Our cryoelectron microscopy (cryo-EM) structures reveal that two crescent-shaped UBR5 monomers assemble head to tail to form the dimer, and two dimers bind face to face to form the cage-like tetramer with all four catalytic HECT domains facing the central cavity. Importantly, the N-terminal region of one subunit and the HECT of the other form an "intermolecular jaw" in the dimer. We show the jaw-lining residues are important for function, suggesting that the intermolecular jaw functions to recruit ubiquitin-loaded E2 to UBR5. Further work is needed to understand how oligomerization regulates UBR5 ligase activity. This work provides a framework for structure-based anticancer drug development and contributes to a growing appreciation of E3 ligase diversity. | |||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 216.8 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 22.1 KB 22.1 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 13.2 KB | Display | ![]() |
Images | ![]() | 76.7 KB | ||
Filedesc metadata | ![]() | 7.8 KB | ||
Others | ![]() ![]() ![]() | 119.9 MB 226.3 MB 226.3 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8d4xMC ![]() 8e0qC ![]() 8ewiC 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
File | ![]() | ||||||||||||||||||||
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Annotation | Primary map | ||||||||||||||||||||
Voxel size | X=Y=Z: 0.828 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Additional map: RAW map
File | emd_27201_additional_1.map | ||||||||||||
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Annotation | RAW map | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Half map A
File | emd_27201_half_map_1.map | ||||||||||||
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Annotation | Half map A | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Half map B
File | emd_27201_half_map_2.map | ||||||||||||
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Annotation | Half map B | ||||||||||||
Projections & Slices |
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Density Histograms |
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Sample components
-Entire : Homodimer of human E3 ligase UBR5
Entire | Name: Homodimer of human E3 ligase UBR5 |
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Components |
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-Supramolecule #1: Homodimer of human E3 ligase UBR5
Supramolecule | Name: Homodimer of human E3 ligase UBR5 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1 / Details: UBR5 expressed in insect cell |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 610 KDa |
-Macromolecule #1: E3 ubiquitin-protein ligase UBR5
Macromolecule | Name: E3 ubiquitin-protein ligase UBR5 / type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO / EC number: HECT-type E3 ubiquitin transferase |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 310.604625 KDa |
Recombinant expression | Organism: Insect expression vector pBlueBachsGCA1 (others) |
Sequence | String: DYKDDDKMTS IHFVVHPLPG TEDQLNDRLR EVSEKLNKYN LNSHPPLNVL EQATIKQCVV GPNHAAFLLE DGRVCRIGFS VQPDRLELG KPDNNDGSKL NSNSGAGRTS RPGRTSDSPW FLSGSETLGR LAGNTLGSRW SSGVGGSGGG SSGRSSAGAR D SRRQTRVI ...String: DYKDDDKMTS IHFVVHPLPG TEDQLNDRLR EVSEKLNKYN LNSHPPLNVL EQATIKQCVV GPNHAAFLLE DGRVCRIGFS VQPDRLELG KPDNNDGSKL NSNSGAGRTS RPGRTSDSPW FLSGSETLGR LAGNTLGSRW SSGVGGSGGG SSGRSSAGAR D SRRQTRVI RTGRDRGSGL LGSQPQPVIP ASVIPEELIS QAQVVLQGKS RSVIIRELQR TNLDVNLAVN NLLSRDDEDG DD GDDTASE SYLPGEDLMS LLDADIHSAH PSVIIDADAM FSEDISYFGY PSFRRSSLSR LGSSRVLLLP LERDSELLRE RES VLRLRE RRWLDGASFD NERGSTSKEG EPNLDKKNTP VQSPVSLGED LQWWPDKDGT KFICIGALYS ELLAVSSKGE LYQW KWSES EPYRNAQNPS LHHPRATFLG LTNEKIVLLS ANSIRATVAT ENNKVATWVD ETLSSVASKL EHTAQTYSEL QGERI VSLH CCALYTCAQL ENSLYWWGVV PFSQRKKMLE KARAKNKKPK SSAGISSMPN ITVGTQVCLR NNPLYHAGAV AFSISA GIP KVGVLMESVW NMNDSCRFQL RSPESLKNME KASKTTEAKP ESKQEPVKTE MGPPPSPAST CSDASSIASS ASMPYKR RR STPAPKEEEK VNEEQWSLRE VVFVEDVKNV PVGKVLKVDG AYVAVKFPGT SSNTNCQNSS GPDADPSSLL QDCRLLRI D ELQVVKTGGT PKVPDCFQRT PKKLCIPEKT EILAVNVDSK GVHAVLKTGN WVRYCIFDLA TGKAEQENNF PTSSIAFLG QNERNVAIFT AGQESPIILR DGNGTIYPMA KDCMGGIRDP DWLDLPPISS LGMGVHSLIN LPANSTIKKK AAVIIMAVEK QTLMQHILR CDYEACRQYL MNLEQAVVLE QNLQMLQTFI SHRCDGNRNI LHACVSVCFP TSNKETKEEE EAERSERNTF A ERLSAVEA IANAISVVSS NGPGNRAGSS SSRSLRLREM MRRSLRAAGL GRHEAGASSS DHQDPVSPPI APPSWVPDPP AM DPDGDID FILAPAVGSL TTAATGTGQG PSTSTIPGPS TEPSVVESKD RKANAHFILK LLCDSVVLQP YLRELLSAKD ARG MTPFMS AVSGRAYPAA ITILETAQKI AKAEISSSEK EEDVFMGMVC PSGTNPDDSP LYVLCCNDTC SFTWTGAEHI NQDI FECRT CGLLESLCCC TECARVCHKG HDCKLKRTSP TAYCDCWEKC KCKTLIAGQK SARLDLLYRL LTATNLVTLP NSRGE HLLL FLVQTVARQT VEHCQYRPPR IREDRNRKTA SPEDSDMPDH DLEPPRFAQL ALERVLQDWN ALKSMIMFGS QENKDP LSA SSRIGHLLPE EQVYLNQQSG TIRLDCFTHC LIVKCTADIL LLDTLLGTLV KELQNKYTPG RREEAIAVTM RFLRSVA RV FVILSVEMAS SKKKNNFIPQ PIGKCKRVFQ ALLPYAVEEL CNVAESLIVP VRMGIARPTA PFTLASTSID AMQGSEEL F SVEPLPPRPS SDQSSSSSQS QSSYIIRNPQ QRRISQSQPV RGRDEEQDDI VSADVEEVEV VEGVAGEEDH HDEQEEHGE ENAEAEGQHD EHDEDGSDME LDLLAAAETE SDSESNHSNQ DNASGRRSVV TAATAGSEAG ASSVPAFFSE DDSQSNDSSD SDSSSSQSD DIEQETFMLD EPLERTTNSS HANGAAQAPR SMQWAVRNTQ HQRAASTAPS STSTPAASSA GLIYIDPSNL R RSGTISTS AAAAAAALEA SNASSYLTSA SSLARAYSIV IRQISDLMGL IPKYNHLVYS QIPAAVKLTY QDAVNLQNYV EE KLIPTWN WMVSIMDSTE AQLRYGSALA SAGDPGHPNH PLHASQNSAR RERMTAREEA SLRTLEGRRR ATLLSARQGM MSA RGDFLN YALSLMRSHN DEHSDVLPVL DVCSLKHVAY VFQALIYWIK AMNQQTTLDT PQLERKRTRE LLELGIDNED SEHE NDDDT NQSATLNDKD DDSLPAETGQ NHPFFRRSDS MTFLGCIPPN PFEVPLAEAI PLADQPHLLQ PNARKEDLFG RPSQG LYSS SASSGKCLME VTVDRNCLEV LPTKMSYAAN LKNVMNMQNR QKKEGEEQPV LPEETESSKP GPSAHDLAAQ LKSSLL AEI GLTESEGPPL TSFRPQCSFM GMVISHDMLL GRWRLSLELF GRVFMEDVGA EPGSILTELG GFEVKESKFR REMEKLR NQ QSRDLSLEVD RDRDLLIQQT MRQLNNHFGR RCATTPMAVH RVKVTFKDEP GEGSGVARSF YTAIAQAFLS NEKLPNLE C IQNANKGTHT SLMQRLRNRG ERDRERERER EMRRSSGLRA GSRRDRDRDF RRQLSIDTRP FRPASEGNPS DDPEPLPAH RQALGERLYP RVQAMQPAFA SKITGMLLEL SPAQLLLLLA SEDSLRARVD EAMELIIAHG RENGADSILD LGLVDSSEKV QQENRKRHG SSRSVVDMDL DDTDDGDDNA PLFYQPGKRG FYTPRPGKNT EARLNCFRNI GRILGLCLLQ NELCPITLNR H VIKVLLGR KVNWHDFAFF DPVMYESLRQ LILASQSSDA DAVFSAMDLA FAIDLCKEEG GGQVELIPNG VNIPVTPQNV YE YVRKYAE HRMLVVAEQP LHAMRKGLLD VLPKNSLEDL TAEDFRLLVN GCGEVNVQML ISFTSFNDES GENAEKLLQF KRW FWSIVE KMSMTERQDL VYFWTSSPSL PASEEGFQPM PSITIRPPDD QHLPTANTCI SRLYVPLYSS KQILKQKLLL AIKT KNFGF V UniProtKB: E3 ubiquitin-protein ligase UBR5 |
-Macromolecule #2: ZINC ION
Macromolecule | Name: ZINC ION / type: ligand / ID: 2 / Number of copies: 6 / Formula: ZN |
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Molecular weight | Theoretical: 65.409 Da |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Concentration | 0.7 mg/mL | ||||||||||||
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Buffer | pH: 7.5 Component:
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Grid | Model: Quantifoil R2/1 / Material: COPPER / Mesh: 300 / Support film - Material: GOLD / Support film - topology: CONTINUOUS / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 30 sec. / Pretreatment - Atmosphere: AIR | ||||||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 279 K / Instrument: FEI VITROBOT MARK IV / Details: blot 2S, blot forth 2. | ||||||||||||
Details | freshly purified UBR5 |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Temperature | Min: 193.0 K / Max: 193.0 K |
Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 65.0 e/Å2 Details: Images were collected in movie-mode at 75 frames per second |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | C2 aperture diameter: 70.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 2.0 µm / Nominal defocus min: 1.0 µm / Nominal magnification: 105000 |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
-Atomic model buiding 1
Refinement | Space: REAL / Protocol: RIGID BODY FIT / Overall B value: 90.94 / Target criteria: Correlation coefficient |
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Output model | ![]() PDB-8d4x: |