+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-15948 | |||||||||||||||
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Title | Human Mre11-Nbs1 complex | |||||||||||||||
Map data | map_sharp | |||||||||||||||
Sample |
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Keywords | DNA repair / complex / HYDROLASE | |||||||||||||||
Function / homology | Function and homology information telomere maintenance via telomere trimming / chromosomal region / telomeric 3' overhang formation / mitochondrial double-strand break repair via homologous recombination / Mre11 complex / negative regulation of double-strand break repair via nonhomologous end joining / blastocyst growth / negative regulation of telomere capping / protection from non-homologous end joining at telomere / meiotic DNA double-strand break formation ...telomere maintenance via telomere trimming / chromosomal region / telomeric 3' overhang formation / mitochondrial double-strand break repair via homologous recombination / Mre11 complex / negative regulation of double-strand break repair via nonhomologous end joining / blastocyst growth / negative regulation of telomere capping / protection from non-homologous end joining at telomere / meiotic DNA double-strand break formation / Sensing of DNA Double Strand Breaks / BRCA1-C complex / regulation of mitotic recombination / R-loop processing / t-circle formation / phosphorylation-dependent protein binding / telomere maintenance in response to DNA damage / homologous chromosome pairing at meiosis / chromatin-protein adaptor activity / single-stranded DNA endodeoxyribonuclease activity / nuclease activity / homologous recombination / DNA strand resection involved in replication fork processing / nuclear inclusion body / DNA double-strand break processing / positive regulation of telomere maintenance / Cytosolic sensors of pathogen-associated DNA / isotype switching / Impaired BRCA2 binding to PALB2 / protein localization to site of double-strand break / HDR through MMEJ (alt-NHEJ) / IRF3-mediated induction of type I IFN / mitotic G2/M transition checkpoint / reciprocal meiotic recombination / positive regulation of kinase activity / sister chromatid cohesion / Defective homologous recombination repair (HRR) due to BRCA1 loss of function / Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function / Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function / mitotic intra-S DNA damage checkpoint signaling / Homologous DNA Pairing and Strand Exchange / Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA) / regulation of DNA-templated DNA replication initiation / Resolution of D-loop Structures through Holliday Junction Intermediates / DNA duplex unwinding / 3'-5'-DNA exonuclease activity / HDR through Single Strand Annealing (SSA) / Impaired BRCA2 binding to RAD51 / double-strand break repair via alternative nonhomologous end joining / mitotic G2 DNA damage checkpoint signaling / Presynaptic phase of homologous DNA pairing and strand exchange / protein K63-linked ubiquitination / neuromuscular process controlling balance / telomere maintenance via telomerase / DNA damage response, signal transduction by p53 class mediator / positive regulation of double-strand break repair via homologous recombination / neuroblast proliferation / meiotic cell cycle / positive regulation of protein autophosphorylation / 3'-5' exonuclease activity / telomere maintenance / intrinsic apoptotic signaling pathway / protein serine/threonine kinase activator activity / Meiotic recombination / DNA Damage/Telomere Stress Induced Senescence / DNA damage checkpoint signaling / DNA endonuclease activity / replication fork / Nonhomologous End-Joining (NHEJ) / G2/M DNA damage checkpoint / double-strand break repair via homologous recombination / HDR through Homologous Recombination (HRR) / PML body / double-strand break repair via nonhomologous end joining / double-strand break repair / Processing of DNA double-strand break ends / Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks / double-stranded DNA binding / manganese ion binding / site of double-strand break / histone binding / chromosome, telomeric region / DNA-binding transcription factor binding / Regulation of TP53 Activity through Phosphorylation / DNA recombination / cell population proliferation / damaged DNA binding / Hydrolases; Acting on ester bonds / regulation of cell cycle / cadherin binding / DNA repair / DNA damage response / negative regulation of apoptotic process / nucleolus / Golgi apparatus / nucleoplasm / identical protein binding / nucleus / cytoplasm / cytosol Similarity search - Function | |||||||||||||||
Biological species | Homo sapiens (human) | |||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 4.13 Å | |||||||||||||||
Authors | Rotheneder M / Stakyte K / Bartho JD / Lammens K / Hopfner KP | |||||||||||||||
Funding support | Germany, 4 items
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Citation | Journal: Mol Cell / Year: 2023 Title: Cryo-EM structure of the Mre11-Rad50-Nbs1 complex reveals the molecular mechanism of scaffolding functions. Authors: Matthias Rotheneder / Kristina Stakyte / Erik van de Logt / Joseph D Bartho / Katja Lammens / Yilan Fan / Aaron Alt / Brigitte Kessler / Christophe Jung / Wynand P Roos / Barbara ...Authors: Matthias Rotheneder / Kristina Stakyte / Erik van de Logt / Joseph D Bartho / Katja Lammens / Yilan Fan / Aaron Alt / Brigitte Kessler / Christophe Jung / Wynand P Roos / Barbara Steigenberger / Karl-Peter Hopfner / Abstract: The DNA double-strand break repair complex Mre11-Rad50-Nbs1 (MRN) detects and nucleolytically processes DNA ends, activates the ATM kinase, and tethers DNA at break sites. How MRN can act both as ...The DNA double-strand break repair complex Mre11-Rad50-Nbs1 (MRN) detects and nucleolytically processes DNA ends, activates the ATM kinase, and tethers DNA at break sites. How MRN can act both as nuclease and scaffold protein is not well understood. The cryo-EM structure of MRN from Chaetomium thermophilum reveals a 2:2:1 complex with a single Nbs1 wrapping around the autoinhibited Mre11 nuclease dimer. MRN has two DNA-binding modes, one ATP-dependent mode for loading onto DNA ends and one ATP-independent mode through Mre11's C terminus, suggesting how it may interact with DSBs and intact DNA. MRNs two 60-nm-long coiled-coil domains form a linear rod structure, the apex of which is assembled by the two joined zinc-hook motifs. Apices from two MRN complexes can further dimerize, forming 120-nm spanning MRN-MRN structures. Our results illustrate the architecture of MRN and suggest how it mechanistically integrates catalytic and tethering functions. | |||||||||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_15948.map.gz | 20.9 MB | EMDB map data format | |
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Header (meta data) | emd-15948-v30.xml emd-15948.xml | 26.1 KB 26.1 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_15948_fsc.xml | 6.8 KB | Display | FSC data file |
Images | emd_15948.png | 65.6 KB | ||
Masks | emd_15948_msk_1.map | 22.2 MB | Mask map | |
Filedesc metadata | emd-15948.cif.gz | 7.4 KB | ||
Others | emd_15948_additional_1.map.gz emd_15948_additional_2.map.gz emd_15948_half_map_1.map.gz emd_15948_half_map_2.map.gz | 10.9 MB 169.7 MB 20.6 MB 20.6 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-15948 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-15948 | HTTPS FTP |
-Validation report
Summary document | emd_15948_validation.pdf.gz | 768 KB | Display | EMDB validaton report |
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Full document | emd_15948_full_validation.pdf.gz | 767.6 KB | Display | |
Data in XML | emd_15948_validation.xml.gz | 13.3 KB | Display | |
Data in CIF | emd_15948_validation.cif.gz | 17 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-15948 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-15948 | HTTPS FTP |
-Related structure data
Related structure data | 8bahMC 7zqyC 7zr1C M: atomic model generated by this map C: citing same article (ref.) |
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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_15948.map.gz / Format: CCP4 / Size: 22.2 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Annotation | map_sharp | ||||||||||||||||||||
Voxel size | X=Y=Z: 1.059 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Mask #1
File | emd_15948_msk_1.map | ||||||||||||
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Density Histograms |
-Additional map: Map unsharpened
File | emd_15948_additional_1.map | ||||||||||||
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Annotation | Map_unsharpened | ||||||||||||
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Density Histograms |
-Additional map: LAFTER Filtered map
File | emd_15948_additional_2.map | ||||||||||||
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Annotation | LAFTER_Filtered_map | ||||||||||||
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Density Histograms |
-Half map: Half map B
File | emd_15948_half_map_1.map | ||||||||||||
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Annotation | Half_map_B | ||||||||||||
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Density Histograms |
-Half map: Half map A
File | emd_15948_half_map_2.map | ||||||||||||
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Annotation | Half_map_A | ||||||||||||
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Density Histograms |
-Sample components
-Entire : Human Mre11-Nbs1 complex
Entire | Name: Human Mre11-Nbs1 complex |
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Components |
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-Supramolecule #1: Human Mre11-Nbs1 complex
Supramolecule | Name: Human Mre11-Nbs1 complex / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#2 Details: Human Mre11-dimer with Nbs1 C-terminal chain bound. |
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Source (natural) | Organism: Homo sapiens (human) |
-Macromolecule #1: Double-strand break repair protein MRE11
Macromolecule | Name: Double-strand break repair protein MRE11 / type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO / EC number: Hydrolases; Acting on ester bonds |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 84.008633 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MSTADALDDE NTFKILVATD IHLGFMEKDA VRGNDTFVTL DEILRLAQEN EVDFILLGGD LFHENKPSRK TLHTCLELLR KYCMGDRPV QFEILSDQSV NFGFSKFPWV NYQDGNLNIS IPVFSIHGNN DDPTGADALC ALDILSCAGF VNHFGRSMSV E KIDISPVL ...String: MSTADALDDE NTFKILVATD IHLGFMEKDA VRGNDTFVTL DEILRLAQEN EVDFILLGGD LFHENKPSRK TLHTCLELLR KYCMGDRPV QFEILSDQSV NFGFSKFPWV NYQDGNLNIS IPVFSIHGNN DDPTGADALC ALDILSCAGF VNHFGRSMSV E KIDISPVL LQKGSTKIAL YGLGSIPDER LYRMFVNKKV TMLRPKEDEN SWFNLFVIHQ NRSKHGSTNF IPEQFLDDFI DL VIWGHEH ECKIAPTKNE QQLFYISQPG SSVVTSLSPG EAVKKHVGLL RIKGRKMNMH KIPLHTVRQF FMEDIVLANH PDI FNPDNP KVTQAIQSFC LEKIEEMLEN AERERLGNSH QPEKPLVRLR VDYSGGFEPF SVLRFSQKFV DRVANPKDII HFFR HREQK EKTGEEINFG KLITKPSEGT TLRVEDLVKQ YFQTAEKNVQ LSLLTERGMG EAVQEFVDKE EKDAIEELVK YQLEK TQRF LKERHIDALE DKIDEEVRRF RETRQKNTNE EDDEVREAMT RARALRSQSE ESASAFSADD LMSIDLAEQM ANDSDD SIS AATNKGRGRG RGRRGGRGQN SASRGGSQRG RADTGLETST RSRNSKTAVS ASRNMSIIDA FKSTRQQPSR NVTTKNY SE VIEVDESDVE EDIFPTTSKT DQRWSSTSSS KIMSQSQVSK GVDFESSEDD DDDPFMNTSS LRRNRRSGGS LEVLFQGP D YKDDDDKGTD YKDDDDK UniProtKB: Double-strand break repair protein MRE11 |
-Macromolecule #2: Nibrin
Macromolecule | Name: Nibrin / 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: 85.073023 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MWKLLPAAGP AGGEPYRLLT GVEYVVGRKN CAILIENDQS ISRNHAVLTA NFSVTNLSQT DEIPVLTLKD NSKYGTFVNE EKMQNGFSR TLKSGDGITF GVFGSKFRIE YEPLVACSSC LDVSGKTALN QAILQLGGFT VNNWTEECTH LVMVSVKVTI K TICALICG ...String: MWKLLPAAGP AGGEPYRLLT GVEYVVGRKN CAILIENDQS ISRNHAVLTA NFSVTNLSQT DEIPVLTLKD NSKYGTFVNE EKMQNGFSR TLKSGDGITF GVFGSKFRIE YEPLVACSSC LDVSGKTALN QAILQLGGFT VNNWTEECTH LVMVSVKVTI K TICALICG RPIVKPEYFT EFLKAVESKK QPPQIESFYP PLDEPSIGSK NVDLSGRQER KQIFKGKTFI FLNAKQHKKL SS AVVFGGG EARLITEENE EEHNFFLAPG TCVVDTGITN SQTLIPDCQK KWIQSIMDML QRQGLRPIPE AEIGLAVIFM TTK NYCDPQ GHPSTGLKTT TPGPSLSQGV SVDEKLMPSA PVNTTTYVAD TESEQADTWD LSERPKEIKV SKMEQKFRML SQDA PTVKE SCKTSSNNNS MVSNTLAKMR IPNYQLSPTK LPSINKSKDR ASQQQQTNSI RNYFQPSTKK RERDEENQEM SSCKS ARIE TSCSLLEQTQ PATPSLWKNK EQHLSENEPV DTNSDNNLFT DTDLKSIVKN SASKSHAAEK LRSNKKREMD DVAIED EVL EQLFKDTKPE LEIDVKVQKQ EEDVNVRKRP RMDIETNDTF SDEAVPESSK ISQENEIGKK RELKEDSLWS AKEISNN DK LQDDSEMLPK KLLLTEFRSL VIKNSTSRNP SGINDDYGQL KNFKKFKKVT YPGAGKLPHI IGGSDLIAHH ARKNTELE E WLRQEMEVQN QHAKEESLAD DLFRYNPYLK RRR UniProtKB: Nibrin |
-Macromolecule #3: MANGANESE (II) ION
Macromolecule | Name: MANGANESE (II) ION / type: ligand / ID: 3 / Number of copies: 4 / Formula: MN |
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Molecular weight | Theoretical: 54.938 Da |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 0.29 mg/mL | |||||||||||||||||||||||||||
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Buffer | pH: 7 Component:
Details: 20 mM HEPES (pH 7.0), 140 mM NaCl, 5 mM MgCl2, 1 mM MnCl2, 0.020 mM ZnCl2, 0.2 mM TCEP, 2 mM ATPgS, plus 0.05 percent beta-OG | |||||||||||||||||||||||||||
Grid | Model: Quantifoil R2/1 / Material: COPPER / Mesh: 200 / Support film - Material: CARBON / Support film - topology: HOLEY / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 7 sec. / Pretreatment - Atmosphere: AIR | |||||||||||||||||||||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 95 % / Chamber temperature: 288 K / Instrument: LEICA EM GP |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Specialist optics | Energy filter - Name: GIF Bioquantum / Energy filter - Slit width: 20 eV |
Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: COUNTING / Number grids imaged: 3 / Number real images: 11325 / Average exposure time: 10.0 sec. / Average electron dose: 43.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | C2 aperture diameter: 50.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 2.8000000000000003 µm / Nominal defocus min: 1.0 µm / Nominal magnification: 13000 |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |