9q9j

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Current revision (06:00, 1 October 2025) (edit) (undo)
 
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'''Unreleased structure'''
 
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The entry 9q9j is ON HOLD until Paper Publication
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==Cryo-EM structure of human Mre11-Rad50-Nbs1 (MRN) complex bound to DNA and telomeric factor TRF2 fragment (438-542)==
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<StructureSection load='9q9j' size='340' side='right'caption='[[9q9j]], [[Resolution|resolution]] 2.71&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[9q9j]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9Q9J OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9Q9J FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.71&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=BEF:BERYLLIUM+TRIFLUORIDE+ION'>BEF</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=9q9j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9q9j OCA], [https://pdbe.org/9q9j PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9q9j RCSB], [https://www.ebi.ac.uk/pdbsum/9q9j PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9q9j ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/TERF2_HUMAN TERF2_HUMAN] Binds the telomeric double-stranded 5'-TTAGGG-3' repeat and plays a central role in telomere maintenance and protection against end-to-end fusion of chromosomes. In addition to its telomeric DNA-binding role, required to recruit a number of factors and enzymes required for telomere protection, including the shelterin complex, TERF2IP/RAP1 and DCLRE1B/Apollo. Component of the shelterin complex (telosome) that is involved in the regulation of telomere length and protection. Shelterin associates with arrays of double-stranded 5'-TTAGGG-3' repeats added by telomerase and protects chromosome ends; without its protective activity, telomeres are no longer hidden from the DNA damage surveillance and chromosome ends are inappropriately processed by DNA repair pathways. Together with DCLRE1B/Apollo, plays a key role in telomeric loop (T loop) formation by generating 3' single-stranded overhang at the leading end telomeres: T loops have been proposed to protect chromosome ends from degradation and repair. Required both to recruit DCLRE1B/Apollo to telomeres and activate the exonuclease activity of DCLRE1B/Apollo. Preferentially binds to positive supercoiled DNA. Together with DCLRE1B/Apollo, required to control the amount of DNA topoisomerase (TOP1, TOP2A and TOP2B) needed for telomere replication during fork passage and prevent aberrant telomere topology. Recruits TERF2IP/RAP1 to telomeres, thereby participating in to repressing homology-directed repair (HDR), which can affect telomere length.<ref>PMID:9476899</ref> <ref>PMID:16166375</ref> <ref>PMID:20655466</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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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.
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Authors:
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Structural basis for DNA break sensing by human MRE11-RAD50-NBS1 and its regulation by telomeric factor TRF2.,Fan Y, Kuybu F, Cui H, Lammens K, Chen JX, Kugler M, Jung C, Hopfner KP Nat Commun. 2025 Sep 18;16(1):8320. doi: 10.1038/s41467-025-64082-x. PMID:40968163<ref>PMID:40968163</ref>
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Description:
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[Category: Unreleased Structures]]
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</div>
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<div class="pdbe-citations 9q9j" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Homo sapiens]]
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[[Category: Large Structures]]
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[[Category: Cui HJ]]
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[[Category: Fan YL]]
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[[Category: Hopfner KP]]
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[[Category: Kuybu F]]
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[[Category: Lammens K]]

Current revision

Cryo-EM structure of human Mre11-Rad50-Nbs1 (MRN) complex bound to DNA and telomeric factor TRF2 fragment (438-542)

PDB ID 9q9j

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