6r92
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Cryo-EM structure of NCP-THF2(+1)-UV-DDB class B== | |
| + | <SX load='6r92' size='340' side='right' viewer='molstar' caption='[[6r92]], [[Resolution|resolution]] 4.80Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6r92]] is a 12 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=6R92 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6R92 FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 4.8Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3DR:1,2-DIDEOXYRIBOFURANOSE-5-PHOSPHATE'>3DR</scene></td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6r92 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6r92 OCA], [https://pdbe.org/6r92 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6r92 RCSB], [https://www.ebi.ac.uk/pdbsum/6r92 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6r92 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
| + | [https://www.uniprot.org/uniprot/DDB2_HUMAN DDB2_HUMAN] Defects in DDB2 are a cause of xeroderma pigmentosum complementation group E (XP-E) [MIM:[https://omim.org/entry/278740 278740]; also known as xeroderma pigmentosum V (XP5). XP-E is a rare human autosomal recessive disease characterized by solar sensitivity, high predisposition for developing cancers on areas exposed to sunlight and, in some cases, neurological abnormalities.<ref>PMID:8798680</ref> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/DDB2_HUMAN DDB2_HUMAN] Required for DNA repair. Binds to DDB1 to form the UV-damaged DNA-binding protein complex (the UV-DDB complex). The UV-DDB complex may recognize UV-induced DNA damage and recruit proteins of the nucleotide excision repair pathway (the NER pathway) to initiate DNA repair. The UV-DDB complex preferentially binds to cyclobutane pyrimidine dimers (CPD), 6-4 photoproducts (6-4 PP), apurinic sites and short mismatches. Also appears to function as the substrate recognition module for the DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complex DDB1-CUL4-ROC1 (also known as CUL4-DDB-ROC1 and CUL4-DDB-RBX1). The DDB1-CUL4-ROC1 complex may ubiquitinate histone H2A, histone H3 and histone H4 at sites of UV-induced DNA damage. The ubiquitination of histones may facilitate their removal from the nucleosome and promote subsequent DNA repair. The DDB1-CUL4-ROC1 complex also ubiquitinates XPC, which may enhance DNA-binding by XPC and promote NER. Isoform D1 and isoform D2 inhibit UV-damaged DNA repair.<ref>PMID:14751237</ref> <ref>PMID:9892649</ref> <ref>PMID:10882109</ref> <ref>PMID:11278856</ref> <ref>PMID:11705987</ref> <ref>PMID:12732143</ref> <ref>PMID:12944386</ref> <ref>PMID:15882621</ref> <ref>PMID:16260596</ref> <ref>PMID:16678110</ref> <ref>PMID:16473935</ref> <ref>PMID:18593899</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Access to DNA packaged in nucleosomes is critical for gene regulation, DNA replication and DNA repair. In humans, the UV-damaged DNA-binding protein (UV-DDB) complex detects UV-light-induced pyrimidine dimers throughout the genome; however, it remains unknown how these lesions are recognized in chromatin, in which nucleosomes restrict access to DNA. Here we report cryo-electron microscopy structures of UV-DDB bound to nucleosomes bearing a 6-4 pyrimidine-pyrimidone dimer or a DNA-damage mimic in various positions. We find that UV-DDB binds UV-damaged nucleosomes at lesions located in the solvent-facing minor groove without affecting the overall nucleosome architecture. In the case of buried lesions that face the histone core, UV-DDB changes the predominant translational register of the nucleosome and selectively binds the lesion in an accessible, exposed position. Our findings explain how UV-DDB detects occluded lesions in strongly positioned nucleosomes, and identify slide-assisted site exposure as a mechanism by which high-affinity DNA-binding proteins can access otherwise occluded sites in nucleosomal DNA. | ||
| - | + | DNA damage detection in nucleosomes involves DNA register shifting.,Matsumoto S, Cavadini S, Bunker RD, Grand RS, Potenza A, Rabl J, Yamamoto J, Schenk AD, Schubeler D, Iwai S, Sugasawa K, Kurumizaka H, Thoma NH Nature. 2019 May 29. pii: 10.1038/s41586-019-1259-3. doi:, 10.1038/s41586-019-1259-3. PMID:31142837<ref>PMID:31142837</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: Bunker | + | <div class="pdbe-citations 6r92" style="background-color:#fffaf0;"></div> |
| - | [[Category: Cavadini | + | |
| - | [[Category: Matsumoto | + | ==See Also== |
| - | [[Category: Thoma | + | *[[DNA damage-binding protein|DNA damage-binding protein]] |
| + | *[[Histone 3D structures|Histone 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </SX> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Bunker RD]] | ||
| + | [[Category: Cavadini S]] | ||
| + | [[Category: Matsumoto S]] | ||
| + | [[Category: Thoma NH]] | ||
Current revision
Cryo-EM structure of NCP-THF2(+1)-UV-DDB class B
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