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Yorodumi- EMDB-21139: Structure of mono-ubiquitinated FANCD2 bound to non-ubiquitinated... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-21139 | |||||||||
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Title | Structure of mono-ubiquitinated FANCD2 bound to non-ubiquitinated FANCI and to DNA. | |||||||||
Map data | consensus reconstruction | |||||||||
Sample |
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Keywords | DNA clamp / DNA BINDING PROTEIN / DNA BINDING PROTEIN-DNA complex | |||||||||
Function / homology | Function and homology information regulation of CD40 signaling pathway / regulation of regulatory T cell differentiation / homologous chromosome pairing at meiosis / gamete generation / double-strand break repair involved in meiotic recombination / neuronal stem cell population maintenance / brain morphogenesis / DNA repair complex / mitotic intra-S DNA damage checkpoint signaling / interstrand cross-link repair ...regulation of CD40 signaling pathway / regulation of regulatory T cell differentiation / homologous chromosome pairing at meiosis / gamete generation / double-strand break repair involved in meiotic recombination / neuronal stem cell population maintenance / brain morphogenesis / DNA repair complex / mitotic intra-S DNA damage checkpoint signaling / interstrand cross-link repair / DNA polymerase binding / condensed chromosome / Maturation of protein E / Maturation of protein E / ER Quality Control Compartment (ERQC) / Myoclonic epilepsy of Lafora / IRAK2 mediated activation of TAK1 complex / Alpha-protein kinase 1 signaling pathway / FLT3 signaling by CBL mutants / IRAK1 recruits IKK complex / IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation / Prevention of phagosomal-lysosomal fusion / Glycogen synthesis / IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation / Regulation of TBK1, IKKε (IKBKE)-mediated activation of IRF3, IRF7 / Endosomal Sorting Complex Required For Transport (ESCRT) / TICAM1,TRAF6-dependent induction of TAK1 complex / Membrane binding and targetting of GAG proteins / Regulation of TBK1, IKKε-mediated activation of IRF3, IRF7 upon TLR3 ligation / Negative regulation of FLT3 / Constitutive Signaling by NOTCH1 HD Domain Mutants / PTK6 Regulates RTKs and Their Effectors AKT1 and DOK1 / Regulation of FZD by ubiquitination / TICAM1-dependent activation of IRF3/IRF7 / NOTCH2 Activation and Transmission of Signal to the Nucleus / p75NTR recruits signalling complexes / APC/C:Cdc20 mediated degradation of Cyclin B / Downregulation of ERBB4 signaling / TRAF6-mediated induction of TAK1 complex within TLR4 complex / TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling / APC-Cdc20 mediated degradation of Nek2A / Regulation of innate immune responses to cytosolic DNA / NF-kB is activated and signals survival / InlA-mediated entry of Listeria monocytogenes into host cells / Regulation of pyruvate metabolism / VLDLR internalisation and degradation / Downregulation of ERBB2:ERBB3 signaling / NRIF signals cell death from the nucleus / Pexophagy / Activated NOTCH1 Transmits Signal to the Nucleus / Regulation of PTEN localization / Regulation of BACH1 activity / Synthesis of active ubiquitin: roles of E1 and E2 enzymes / TICAM1, RIP1-mediated IKK complex recruitment / Translesion synthesis by REV1 / MAP3K8 (TPL2)-dependent MAPK1/3 activation / Translesion synthesis by POLK / Downregulation of TGF-beta receptor signaling / Activation of IRF3, IRF7 mediated by TBK1, IKKε (IKBKE) / Translesion synthesis by POLI / PINK1-PRKN Mediated Mitophagy / IKK complex recruitment mediated by RIP1 / Regulation of activated PAK-2p34 by proteasome mediated degradation / JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1 / Gap-filling DNA repair synthesis and ligation in GG-NER / Josephin domain DUBs / InlB-mediated entry of Listeria monocytogenes into host cell / TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition) / positive regulation of protein ubiquitination / TNFR1-induced NF-kappa-B signaling pathway / N-glycan trimming in the ER and Calnexin/Calreticulin cycle / Autodegradation of Cdh1 by Cdh1:APC/C / APC/C:Cdc20 mediated degradation of Securin / Regulation of NF-kappa B signaling / SCF-beta-TrCP mediated degradation of Emi1 / Asymmetric localization of PCP proteins / TCF dependent signaling in response to WNT / NIK-->noncanonical NF-kB signaling / Ubiquitin-dependent degradation of Cyclin D / AUF1 (hnRNP D0) binds and destabilizes mRNA / activated TAK1 mediates p38 MAPK activation / TNFR2 non-canonical NF-kB pathway / Vpu mediated degradation of CD4 / Negative regulators of DDX58/IFIH1 signaling / TP53 Regulates Transcription of DNA Repair Genes / NOTCH3 Activation and Transmission of Signal to the Nucleus / response to gamma radiation / Assembly of the pre-replicative complex / Degradation of DVL / Deactivation of the beta-catenin transactivating complex / Ubiquitin Mediated Degradation of Phosphorylated Cdc25A / Regulation of signaling by CBL / Dectin-1 mediated noncanonical NF-kB signaling / Cdc20:Phospho-APC/C mediated degradation of Cyclin A / Fanconi Anemia Pathway / Negative regulation of FGFR3 signaling / Hh mutants are degraded by ERAD / Degradation of AXIN / Peroxisomal protein import / Activation of NF-kappaB in B cells Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.9 Å | |||||||||
Authors | Pavletich NP | |||||||||
Funding support | United States, 1 items
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Citation | Journal: Nature / Year: 2020 Title: DNA clamp function of the monoubiquitinated Fanconi anaemia ID complex. Authors: Renjing Wang / Shengliu Wang / Ankita Dhar / Christopher Peralta / Nikola P Pavletich / Abstract: The ID complex, involving the proteins FANCI and FANCD2, is required for the repair of DNA interstrand crosslinks (ICL) and related lesions. These proteins are mutated in Fanconi anaemia, a disease ...The ID complex, involving the proteins FANCI and FANCD2, is required for the repair of DNA interstrand crosslinks (ICL) and related lesions. These proteins are mutated in Fanconi anaemia, a disease in which patients are predisposed to cancer. The Fanconi anaemia pathway of ICL repair is activated when a replication fork stalls at an ICL; this triggers monoubiquitination of the ID complex, in which one ubiquitin molecule is conjugated to each of FANCI and FANCD2. Monoubiquitination of ID is essential for ICL repair by excision, translesion synthesis and homologous recombination; however, its function remains unknown. Here we report a cryo-electron microscopy structure of the monoubiquitinated human ID complex bound to DNA, and reveal that it forms a closed ring that encircles the DNA. By comparison with the structure of the non-ubiquitinated ID complex bound to ICL DNA-which we also report here-we show that monoubiquitination triggers a complete rearrangement of the open, trough-like ID structure through the ubiquitin of one protomer binding to the other protomer in a reciprocal fashion. These structures-together with biochemical data-indicate that the monoubiquitinated ID complex loses its preference for ICL and related branched DNA structures, and becomes a sliding DNA clamp that can coordinate the subsequent repair reactions. Our findings also reveal how monoubiquitination in general can induce an alternative protein structure with a new function. | |||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_21139.map.gz | 59.9 MB | EMDB map data format | |
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Header (meta data) | emd-21139-v30.xml emd-21139.xml | 24.5 KB 24.5 KB | Display Display | EMDB header |
Images | emd_21139.png | 131 KB | ||
Filedesc metadata | emd-21139.cif.gz | 7.5 KB | ||
Others | emd_21139_additional_1.map.gz emd_21139_additional_2.map.gz emd_21139_additional_3.map.gz emd_21139_additional_4.map.gz | 60 MB 60 MB 59.9 MB 1.8 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-21139 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-21139 | HTTPS FTP |
-Validation report
Summary document | emd_21139_validation.pdf.gz | 554.8 KB | Display | EMDB validaton report |
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Full document | emd_21139_full_validation.pdf.gz | 554.4 KB | Display | |
Data in XML | emd_21139_validation.xml.gz | 6 KB | Display | |
Data in CIF | emd_21139_validation.cif.gz | 6.8 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-21139 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-21139 | HTTPS FTP |
-Related structure data
Related structure data | 6vafMC 6vaaC 6vadC 6vaeC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_21139.map.gz / Format: CCP4 / Size: 64 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | consensus reconstruction | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.08847 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Additional map: focus1 map
File | emd_21139_additional_1.map | ||||||||||||
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Annotation | focus1 map | ||||||||||||
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Density Histograms |
-Additional map: focus2 map
File | emd_21139_additional_2.map | ||||||||||||
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Annotation | focus2 map | ||||||||||||
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Density Histograms |
-Additional map: focus3 map
File | emd_21139_additional_3.map | ||||||||||||
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Annotation | focus3 map | ||||||||||||
Projections & Slices |
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Density Histograms |
-Additional map: refmac composite map
File | emd_21139_additional_4.map | ||||||||||||
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Annotation | refmac composite map | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Mono-ubiquitinated FANCD2 bound to non-ubiquitinated FANCI and to DNA
Entire | Name: Mono-ubiquitinated FANCD2 bound to non-ubiquitinated FANCI and to DNA |
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Components |
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-Supramolecule #1: Mono-ubiquitinated FANCD2 bound to non-ubiquitinated FANCI and to DNA
Supramolecule | Name: Mono-ubiquitinated FANCD2 bound to non-ubiquitinated FANCI and to DNA type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: Homo sapiens (human) |
-Macromolecule #1: Fanconi anemia, complementation group I
Macromolecule | Name: Fanconi anemia, complementation group I / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 149.566047 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: MDQKILSLAA EKTADKLQEF LQTLREGDLT NLLQNQAVKG KVAGALLRAI FKGSPCSEEA GTLRRRKIYT CCIQLVESGD LQKEIVSEI IGLLMLEAHH FPGPLLVELA NEFISAVREG SLVNGKSLEL LPIILTVLAT KKENLAYGKG VLSGEECKKQ L INTLCSGR ...String: MDQKILSLAA EKTADKLQEF LQTLREGDLT NLLQNQAVKG KVAGALLRAI FKGSPCSEEA GTLRRRKIYT CCIQLVESGD LQKEIVSEI IGLLMLEAHH FPGPLLVELA NEFISAVREG SLVNGKSLEL LPIILTVLAT KKENLAYGKG VLSGEECKKQ L INTLCSGR WDQQYVIQLT SMFKDVPLTA EEVEFVVEKA LSMFSKMNLQ EIPPLVYQLL VLSSKGSRKS VLEGIIAFFS AL DKQHNEE QSGDELLDVV TVPSGELRHV EGTIILHIVF AIKLDYELGR ELVKHLKVGQ QGDSNNNLSP FSIALLLSVT RIQ RFQDQV LDLLKTSVVK SFKDLQLLQG SKFLQNLVPH RSYVSTMILE VVKNSVHSWD HVTQGLVELG FILMDSYGPK KVLD GKTIE TSPSLSRMPN QHACKLGANI LLETFKIHEM IRQEILEQVL NRVVTRASSP ISHFLDLLSN IVMYAPLVLQ NCSSK VTEA FDYLSFLPLQ TVQRLLKAVQ PLLKVSMSMR DCLILVLRKA MFANQLDARK SAVAGFLLLL KNFKVLGSLS SSQCSQ SLS VSQVHVDVHS HYNSVANETF CLEIMDSLRR CLSQQADVRL MLYEGFYDVL RRNSQLANSV MQTLLSQLKQ FYEPEPD LL PPLKLEACIL TQGDQISLQE PLDYLLCCIQ HCLAWYKNTV IPLQQGEEEE EEEEAFYEDL DDILESITNR MIKSELED F ELDKSADFSQ STSIGIKNNI SAFLVMGVCE VLIEYNFSIS SFSKNRFEDI LSLFMCYKKL SDILNEKAGK AKTKMANKT SDSLLSMKFV SSLLTALFRD SIQSHQESLS VLRSSNEFMR YAVNVALQKV QQLKETGHVS GPDGQNPEKI FQNLCDLTRV LLWRYTSIP TSVEESGKKE KGKSISLLCL EGLQKIFSAV QQFYQPKIQQ FLRALDVTDK EGEEREDADV SVTQRTAFQI R QFQRSLLN LLSSQEEDFN SKEALLLVTV LTSLSKLLEP SSPQFVQMLS WTSKICKENS REDALFCKSL MNLLFSLHVS YK SPVILLR DLSQDIHGHL GDIDQDVEVE KTNHFAIVNL RTAAPTVCLL VLSQAEKVLE EVDWLITKLK GQVSQETLSE EAS SQATLP NQPVEKAIIM QLGTLLTFFH ELVQTALPSG SCVDTLLKDL CKMYTTLTAL VRYYLQVCQS SGGIPKNMEK LVKL SGSHL TPLCYSFISY VQNKSKSLNY TGEKKEKPAV VATAMARVLR ETKPIPNLIF AIEQYEKFLI HLSKKSKVSL MQHMK LSTS RDFKIKGNIL DMVLREDGED ENEEGTASEH GGQNKEPAKK KRKK UniProtKB: Fanconi anemia, complementation group I |
-Macromolecule #2: Fanconi anemia group D2 protein
Macromolecule | Name: Fanconi anemia group D2 protein / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 164.314516 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: MVSKRRLSKS EDKESLTEDA SKTRKQPLSK KTKKSHIANE VEENDSIFVK LLKISGIILK TGESQNQLAV DQIAFQKKLF QTLRRHPSY PKIIEEFVSG LESYIEDEDS FRNCLLSCER LQDEEASMGA SYSKSLIKLL LGIDILQPAI IKTLFEKLPE Y FFENKNSD ...String: MVSKRRLSKS EDKESLTEDA SKTRKQPLSK KTKKSHIANE VEENDSIFVK LLKISGIILK TGESQNQLAV DQIAFQKKLF QTLRRHPSY PKIIEEFVSG LESYIEDEDS FRNCLLSCER LQDEEASMGA SYSKSLIKLL LGIDILQPAI IKTLFEKLPE Y FFENKNSD EINIPRLIVS QLKWLDRVVD GKDLTTKIMQ LISIAPENLQ HDIITSLPEI LGDSQHADVG KELSDLLIEN TS LTVPILD VLSSLRLDPN FLLKVRQLVM DKLSSIRLED LPVIIKFILH SVTAMDTLEV ISELREKLDL QHCVLPSRLQ ASQ VKLKSK GRASSSGNQE SSGQSCIILL FDVIKSAIRY EKTISEAWIK AIENTASVSE HKVFDLVMLF IIYSTNTQTK KYID RVLRN KIRSGCIQEQ LLQSTFSVHY LVLKDMCSSI LSLAQSLLHS LDQSIISFGS LLYKYAFKFF DTYCQQEVVG ALVTH ICSG NEAEVDTALD VLLELVVLNP SAMMMNAVFV KGILDYLDNI SPQQIRKLFY VLSTLAFSKQ NEASSHIQDD MHLVIR KQL SSTVFKYKLI GIIGAVTMAG IMAADRSESP SLTQERANLS DEQCTQVTSL LQLVHSCSEQ SPQASALYYD EFANLIQ HE KLDPKALEWV GQTICNDFQD AFVVDSCVVP EGDFPFPVKA LYGLEEYDTQ NGIAINLLPL LFSQDFAKDG GPVTSQES G QKLVSPLCLA PYFRLLRLCV ERQHNGNLEE IDGLLDCPIF LTDLEPGEKL ESMSAKERSF MCSLIFLTLN WFREIVNAF CQETSPEMKG KVLTRLKHIV ELQIILEKYL AVTPDYVPPL GNFDVETLDI TPHTVTAISA KIRKKGKIER KQKTDGSKTS SSDTLSEEK NSECDPTPSH RGQLNKEFTG KEEKTSLLLH NSHAFFRELD IEVFSILHCG LVTKFILDTE MHTEATEVVQ L GPPELLFL LEDLSQKLES MLTPPIARRV PFLKNKGSRN IGFSHLQQRS AQEIVHCVFQ LLTPMCNHLE NIHNYFQCLA AE NHGVVDG PGVKVQEYHI MSSCYQRLLQ IFHGLFAWSG FSQPENQNLL YSALHVLSSR LKQGEHSQPL EELLSQSVHY LQN FHQSIP SFQCALYLIR LLMVILEKST ASAQNKEKIA SLARQFLCRV WPSGDKEKSN ISNDQLHALL CIYLEHTESI LKAI EEIAG VGVPELINSP KDASSSTFPT LTRHTFVVFF RVMMAELEKT VKKIEPGTAA DSQQIHEEKL LYWNMAVRDF SILIN LIKV FDSHPVLHVC LKYGRLFVEA FLKQCMPLLD FSFRKHREDV LSLLETFQLD TRLLHHLCGH SKIHQDTRLT QHVPLL KKT LELLVCRVKA MLTLNNCREA FWLGNLKNRD LQGEEIKSQN SQESTADESE DDMSSQASKS KATEDGEEDE VSAGEKE QD SDESYDDSD UniProtKB: Fanconi anemia group D2 protein |
-Macromolecule #3: Ubiquitin
Macromolecule | Name: Ubiquitin / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 8.576831 KDa |
Recombinant expression | Organism: Escherichia coli (E. coli) |
Sequence | String: MQIFVKTLTG KTITLEVEPS DTIENVKAKI QDKEGIPPDQ QRLIFAGKQL EDGRTLSDYN IQKESTLHLV LRLRGG UniProtKB: Polyubiquitin-C |
-Macromolecule #4: DNA (29-MER)
Macromolecule | Name: DNA (29-MER) / type: dna / ID: 4 / Number of copies: 1 / Classification: DNA |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 8.951746 KDa |
Sequence | String: (DG)(DG)(DC)(DA)(DC)(DA)(DG)(DG)(DT)(DT) (DC)(DA)(DG)(DA)(DG)(DC)(DA)(DG)(DG)(DC) (DG)(DT)(DT)(DC)(DC)(DG)(DT)(DT)(DC) |
-Macromolecule #5: DNA (29-MER)
Macromolecule | Name: DNA (29-MER) / type: dna / ID: 5 / Number of copies: 1 / Classification: DNA |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 8.880711 KDa |
Sequence | String: (DG)(DA)(DA)(DC)(DG)(DG)(DA)(DA)(DC)(DG) (DC)(DC)(DT)(DG)(DC)(DT)(DC)(DT)(DG)(DA) (DA)(DC)(DC)(DT)(DG)(DT)(DG)(DC)(DC) |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 8 |
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Grid | Details: unspecified |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 51.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Startup model | Type of model: PDB ENTRY |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.9 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 57993 |
Initial angle assignment | Type: MAXIMUM LIKELIHOOD / Software - Name: RELION (ver. 3) |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |