[English] 日本語
Yorodumi
- PDB-9q9k: Cryo-EM structure of human Mre11-Rad50 (MR) complex bound to DNA ... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 9q9k
TitleCryo-EM structure of human Mre11-Rad50 (MR) complex bound to DNA and telomeric factor TRF2 fragment (438-542)
Components
  • (DNA (64-MER)) x 2
  • DNA repair protein RAD50
  • Double-strand break repair protein MRE11
  • Telomeric repeat-binding factor 2
KeywordsHYDROLASE / Mre11-Rad50-TRF2 complex / double-strand DNA break repair protein / nuclease
Function / homology
Function and homology information


chromosomal region / axonal transport of messenger ribonucleoprotein complex / negative regulation of telomere single strand break repair / telomeric 3' overhang formation / negative regulation of telomere maintenance via recombination / telomeric loop formation / mitochondrial double-strand break repair via homologous recombination / Mre11 complex / negative regulation of telomere maintenance via semi-conservative replication / negative regulation of telomeric D-loop disassembly ...chromosomal region / axonal transport of messenger ribonucleoprotein complex / negative regulation of telomere single strand break repair / telomeric 3' overhang formation / negative regulation of telomere maintenance via recombination / telomeric loop formation / mitochondrial double-strand break repair via homologous recombination / Mre11 complex / negative regulation of telomere maintenance via semi-conservative replication / negative regulation of telomeric D-loop disassembly / negative regulation of double-strand break repair via nonhomologous end joining / negative regulation of telomere capping / BRCA1-C complex / Sensing of DNA Double Strand Breaks / meiotic DNA double-strand break formation / protection from non-homologous end joining at telomere / regulation of mitotic recombination / RNA-templated DNA biosynthetic process / R-loop processing / Hydrolases; Acting on acid anhydrides / negative regulation of telomere maintenance / negative regulation of t-circle formation / telomeric D-loop disassembly / single-stranded DNA endodeoxyribonuclease activity / chromosome organization involved in meiotic cell cycle / shelterin complex / Telomere C-strand synthesis initiation / homologous chromosome pairing at meiosis / regulation of telomere maintenance via telomerase / double-stranded telomeric DNA binding / DNA strand resection involved in replication fork processing / nuclease activity / homologous recombination / G-quadruplex DNA binding / 3'-5'-DNA exonuclease activity / DNA double-strand break processing / Telomere C-strand (Lagging Strand) Synthesis / single-stranded telomeric DNA binding / nuclear telomere cap complex / Impaired BRCA2 binding to PALB2 / G-rich strand telomeric DNA binding / telomere capping / telomere maintenance via recombination / Cytosolic sensors of pathogen-associated DNA / mitotic G2/M transition checkpoint / HDR through MMEJ (alt-NHEJ) / Processive synthesis on the C-strand of the telomere / Polymerase switching on the C-strand of the telomere / IRF3-mediated induction of type I IFN / Removal of the Flap Intermediate from the C-strand / reciprocal meiotic recombination / mitotic intra-S DNA damage checkpoint signaling / regulation of telomere maintenance / negative regulation of telomere maintenance via telomere lengthening / sister chromatid cohesion / Homologous DNA Pairing and Strand Exchange / 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 / protein localization to chromosome, telomeric region / Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA) / Resolution of D-loop Structures through Holliday Junction Intermediates / HDR through Single Strand Annealing (SSA) / positive regulation of double-strand break repair / telomeric DNA binding / Impaired BRCA2 binding to RAD51 / negative regulation of telomere maintenance via telomerase / mitotic G2 DNA damage checkpoint signaling / positive regulation of telomere maintenance / Presynaptic phase of homologous DNA pairing and strand exchange / negative regulation of cellular senescence / Telomere Extension By Telomerase / telomere maintenance via telomerase / Packaging Of Telomere Ends / Recognition and association of DNA glycosylase with site containing an affected purine / Cleavage of the damaged purine / 3'-5' exonuclease activity / Recognition and association of DNA glycosylase with site containing an affected pyrimidine / Cleavage of the damaged pyrimidine / telomere maintenance / Inhibition of DNA recombination at telomere / Meiotic synapsis / replication fork / protein serine/threonine kinase activator activity / condensed nuclear chromosome / DNA endonuclease activity / male germ cell nucleus / double-strand break repair via homologous recombination / Nonhomologous End-Joining (NHEJ) / HDR through Homologous Recombination (HRR) / G2/M DNA damage checkpoint / PML body / DNA Damage/Telomere Stress Induced Senescence / double-strand break repair via nonhomologous end joining / Meiotic recombination / cellular senescence / Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks / site of double-strand break / double-strand break repair / manganese ion binding
Similarity search - Function
DNA repair protein Rad50, eukaryotes / Telomeric repeat-binding factor 2, Rap1-binding domain / Telomeric repeat-binding factor 2 Rap1-binding motif / Telomeric repeat-binding factor 2 / DNA double-strand break repair protein Mre11 / Mre11, DNA-binding / Mre11, capping domain / Mre11 DNA-binding presumed domain / Mre11 DNA-binding presumed domain / Rad50 zinc hook motif ...DNA repair protein Rad50, eukaryotes / Telomeric repeat-binding factor 2, Rap1-binding domain / Telomeric repeat-binding factor 2 Rap1-binding motif / Telomeric repeat-binding factor 2 / DNA double-strand break repair protein Mre11 / Mre11, DNA-binding / Mre11, capping domain / Mre11 DNA-binding presumed domain / Mre11 DNA-binding presumed domain / Rad50 zinc hook motif / RAD50, zinc hook / Rad50 zinc-hook domain profile. / Telomeric repeat-binding factor 1/2 / Telomere repeat-binding factor, dimerisation domain superfamily / Telomere repeat-binding factor, dimerisation domain / Telomere repeat binding factor (TRF) / Mre11 nuclease, N-terminal metallophosphatase domain / SbcC/RAD50-like, Walker B motif / Rad50/SbcC-type AAA domain / AAA domain / Myb-type HTH DNA-binding domain profile. / Myb domain / Myb-like DNA-binding domain / Calcineurin-like phosphoesterase domain, ApaH type / Calcineurin-like phosphoesterase / Metallo-dependent phosphatase-like / SANT SWI3, ADA2, N-CoR and TFIIIB'' DNA-binding domains / SANT/Myb domain / Homeobox-like domain superfamily / P-loop containing nucleoside triphosphate hydrolase
Similarity search - Domain/homology
ADENOSINE-5'-DIPHOSPHATE / BERYLLIUM TRIFLUORIDE ION / : / DNA / DNA (> 10) / Double-strand break repair protein MRE11 / Telomeric repeat-binding factor 2 / DNA repair protein RAD50
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.59 Å
AuthorsCui, H.J. / Lammens, K. / Hopfner, K.P. / Fan, Y.L. / Kuybu, F.
Funding support Germany, 1items
OrganizationGrant numberCountry
German Research Foundation (DFG) Germany
CitationJournal: Nat Commun / Year: 2025
Title: Structural basis for DNA break sensing by human MRE11-RAD50-NBS1 and its regulation by telomeric factor TRF2.
Authors: Yilan Fan / Filiz Kuybu / Hengjun Cui / Katja Lammens / Jia-Xuan Chen / Michael Kugler / Christophe Jung / Karl-Peter Hopfner /
Abstract: The MRE11-RAD50-NBS1 (MRN) complex is a central, multifunctional factor in the detection, signaling and nucleolytic processing of DNA double-strand breaks (DSBs). To clarify how human MRN binds ...The MRE11-RAD50-NBS1 (MRN) complex is a central, multifunctional factor in the detection, signaling and nucleolytic processing of DNA double-strand breaks (DSBs). To clarify how human MRN binds generic and telomeric DNA ends and can separate DNA end sensing from nuclease activities, we determined cryo-electron microscopy (cryo-EM) structures of human MRN bound to DNA and to DNA and the telomere protection factor TRF2. MRN senses DSBs through a tight clamp-like sensing state with closed coiled-coil domains, but auto-inhibited MRE11 nuclease. NBS1 wraps around the MRE11 dimer, with NBS1's ATM recruitment motif sequestered by binding to the regulatory RAD50 S site, necessitating a switch in the NBS1 C helix for ATM activation. At telomeric DNA, TRF2 blocks the second S site via the iDDR motif to prevent nuclease and ATM activation. Our results provide a structural framework for DNA sensing via a gating mechanism and separation of sensing, signaling and processing activities of mammalian MRN.
History
DepositionFeb 26, 2025Deposition site: PDBE / Processing site: PDBE
Revision 1.0Oct 1, 2025Provider: repository / Type: Initial release

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
J: Telomeric repeat-binding factor 2
K: Telomeric repeat-binding factor 2
P: DNA (64-MER)
T: DNA (64-MER)
A: DNA repair protein RAD50
B: DNA repair protein RAD50
D: Double-strand break repair protein MRE11
E: Double-strand break repair protein MRE11
hetero molecules


Theoretical massNumber of molelcules
Total (without water)542,90718
Polymers541,6528
Non-polymers1,25510
Water1086
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: electron microscopy, not applicable
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1

-
Components

-
Protein , 3 types, 6 molecules JKABDE

#1: Protein Telomeric repeat-binding factor 2 / TTAGGG repeat-binding factor 2 / Telomeric DNA-binding protein


Mass: 12931.349 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Details: GP is the leftover sequence from PreScission cleavage site, and GGSSGGSSG is a linker sequence between the cleavage site and TRF2(438-542) fragment.
Source: (gene. exp.) Homo sapiens (human) / Gene: TERF2, TRBF2, TRF2 / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: Q15554
#4: Protein DNA repair protein RAD50


Mass: 154150.016 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: RAD50 / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: Q92878
#5: Protein Double-strand break repair protein MRE11 / Meiotic recombination 11 homolog 1 / MRE11 homolog 1 / Meiotic recombination 11 homolog A / MRE11 homolog A


Mass: 84032.680 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Details: Following residue R708 is a short GS linker, a PreScission cleavage site, and two FLAG tags.
Source: (gene. exp.) Homo sapiens (human) / Gene: MRE11, HNGS1, MRE11A / Production host: Trichoplusia ni (cabbage looper)
References: UniProt: P49959, Hydrolases; Acting on ester bonds

-
DNA chain , 2 types, 2 molecules PT

#2: DNA chain DNA (64-MER)


Mass: 19423.369 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) Homo sapiens (human)
#3: DNA chain DNA (64-MER)


Mass: 20000.281 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) Homo sapiens (human)

-
Non-polymers , 5 types, 16 molecules

#6: Chemical ChemComp-ADP / ADENOSINE-5'-DIPHOSPHATE


Mass: 427.201 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C10H15N5O10P2 / Feature type: SUBJECT OF INVESTIGATION / Comment: ADP, energy-carrying molecule*YM
#7: Chemical ChemComp-MG / MAGNESIUM ION


Mass: 24.305 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: Mg / Feature type: SUBJECT OF INVESTIGATION
#8: Chemical ChemComp-BEF / BERYLLIUM TRIFLUORIDE ION


Mass: 66.007 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: BeF3 / Feature type: SUBJECT OF INVESTIGATION
#9: Chemical
ChemComp-MN / MANGANESE (II) ION


Mass: 54.938 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: Mn / Feature type: SUBJECT OF INVESTIGATION
#10: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 6 / Source method: isolated from a natural source / Formula: H2O

-
Details

Has ligand of interestY
Has protein modificationN

-
Experimental details

-
Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

-
Sample preparation

ComponentName: MR-TRF2(438-542)-DNA complex / Type: COMPLEX / Entity ID: #1-#5 / Source: RECOMBINANT
Molecular weightValue: 0.52 MDa / Experimental value: NO
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)Organism: Trichoplusia ni (cabbage looper)
Buffer solutionpH: 7.5
Details: 25mM Hepes-NaOH, pH 7.5, 150 mM NaCl, 1 mM DTT, 1 mM ATP, 1mM BeF3, 5 mM MgCl2, 1 mM MnCl2
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
Specimen supportDetails: 20 mA, 7 s / Grid material: COPPER / Grid mesh size: 200 divisions/in. / Grid type: Quantifoil R2/1
VitrificationInstrument: LEICA PLUNGER / Cryogen name: ETHANE / Humidity: 95 % / Chamber temperature: 283 K

-
Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: TFS KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELD / Nominal defocus max: 2600 nm / Nominal defocus min: 500 nm / Cs: 2.7 mm
Specimen holderCryogen: NITROGEN
Image recordingElectron dose: 40 e/Å2 / Detector mode: COUNTING / Film or detector model: FEI FALCON IV (4k x 4k)
EM imaging opticsEnergyfilter name: GIF Bioquantum / Energyfilter slit width: 20 eV
Image scansMovie frames/image: 40

-
Processing

EM software
IDNameVersionCategory
1cryoSPARC4.6.2particle selection
2EPU3.9.1.8206image acquisition
4cryoSPARC4.6.2CTF correction
7UCSF ChimeraX1.9model fitting
9PHENIX1.20.1model refinement
10cryoSPARC4.6.2initial Euler assignment
11cryoSPARC4.6.2final Euler assignment
12cryoSPARC4.6.2classification
13cryoSPARC4.6.23D reconstruction
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
3D reconstructionResolution: 2.59 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 274928 / Symmetry type: POINT
Atomic model buildingProtocol: RIGID BODY FIT / Space: REAL
Atomic model buildingSource name: AlphaFold / Type: in silico model

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more