3ei1: Difference between revisions
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==Structure of hsDDB1-drDDB2 bound to a 14 bp 6-4 photoproduct containing DNA-duplex== | ==Structure of hsDDB1-drDDB2 bound to a 14 bp 6-4 photoproduct containing DNA-duplex== | ||
<StructureSection load='3ei1' size='340' side='right' caption='[[3ei1]], [[Resolution|resolution]] 2.80Å' scene=''> | <StructureSection load='3ei1' size='340' side='right' caption='[[3ei1]], [[Resolution|resolution]] 2.80Å' scene=''> | ||
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3ei2|3ei2]], [[3ei3|3ei3]], [[3ei4|3ei4]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3ei2|3ei2]], [[3ei3|3ei3]], [[3ei4|3ei4]]</td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DDB1, XAP1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), ddb2, si:dkey-45f10.3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=7955 Brachidanio rerio])</td></tr> | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DDB1, XAP1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), ddb2, si:dkey-45f10.3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=7955 Brachidanio rerio])</td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3ei1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ei1 OCA], [http://pdbe.org/3ei1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3ei1 RCSB], [http://www.ebi.ac.uk/pdbsum/3ei1 PDBsum]</span></td></tr> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3ei1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ei1 OCA], [http://pdbe.org/3ei1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3ei1 RCSB], [http://www.ebi.ac.uk/pdbsum/3ei1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3ei1 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
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Check<jmol> | Check<jmol> | ||
<jmolCheckbox> | <jmolCheckbox> | ||
<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ei/3ei1_consurf.spt"</scriptWhenChecked> | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ei/3ei1_consurf.spt"</scriptWhenChecked> | ||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | ||
<text>to colour the structure by Evolutionary Conservation</text> | <text>to colour the structure by Evolutionary Conservation</text> | ||
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[[Category: Scrima, A]] | [[Category: Scrima, A]] | ||
[[Category: Thoma, N H]] | [[Category: Thoma, N H]] | ||
[[Category: Alternative splicing]] | |||
[[Category: Ddb]] | [[Category: Ddb]] | ||
[[Category: Disease mutation]] | [[Category: Disease mutation]] | ||
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[[Category: Nucleus]] | [[Category: Nucleus]] | ||
[[Category: Phosphoprotein]] | [[Category: Phosphoprotein]] | ||
[[Category: Polymorphism]] | |||
[[Category: Ubl conjugation pathway]] | [[Category: Ubl conjugation pathway]] | ||
[[Category: Uv-damage]] | [[Category: Uv-damage]] | ||
[[Category: Wd repeat]] | [[Category: Wd repeat]] | ||
[[Category: Xeroderma pigmentosum]] | [[Category: Xeroderma pigmentosum]] | ||
Revision as of 00:49, 3 December 2018
Structure of hsDDB1-drDDB2 bound to a 14 bp 6-4 photoproduct containing DNA-duplexStructure of hsDDB1-drDDB2 bound to a 14 bp 6-4 photoproduct containing DNA-duplex
Structural highlights
Function[DDB1_HUMAN] Required for DNA repair. Binds to DDB2 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 a component of numerous distinct DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes which mediate the ubiquitination and subsequent proteasomal degradation of target proteins. The functional specificity of the DCX E3 ubiquitin-protein ligase complex is determined by the variable substrate recognition component recruited by DDB1. DCX(DDB2) (also known as DDB1-CUL4-ROC1, CUL4-DDB-ROC1 and CUL4-DDB-RBX1) 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. DCX(DDB2) also ubiquitinates XPC, which may enhance DNA-binding by XPC and promote NER. DCX(DTL) plays a role in PCNA-dependent polyubiquitination of CDT1 and MDM2-dependent ubiquitination of TP53 in response to radiation-induced DNA damage and during DNA replication. DCX(ERCC8) (the CSA complex) plays a role in transcription-coupled repair (TCR). May also play a role in ubiquitination of CDKN1B/p27kip when associated with CUL4 and SKP2.[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [DDB2_DANRE] 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. Also appears to function as the substrate recognition module for a DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complex which 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 (By similarity). Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedUltraviolet (UV) light-induced pyrimidine photodimers are repaired by the nucleotide excision repair pathway. Photolesions have biophysical parameters closely resembling undamaged DNA, impeding discovery through damage surveillance proteins. The DDB1-DDB2 complex serves in the initial detection of UV lesions in vivo. Here we present the structures of the DDB1-DDB2 complex alone and bound to DNA containing either a 6-4 pyrimidine-pyrimidone photodimer (6-4PP) lesion or an abasic site. The structure shows that the lesion is held exclusively by the WD40 domain of DDB2. A DDB2 hairpin inserts into the minor groove, extrudes the photodimer into a binding pocket, and kinks the duplex by approximately 40 degrees. The tightly localized probing of the photolesions, combined with proofreading in the photodimer pocket, enables DDB2 to detect lesions refractory to detection by other damage surveillance proteins. The structure provides insights into damage recognition in chromatin and suggests a mechanism by which the DDB1-associated CUL4 ubiquitin ligase targets proteins surrounding the site of damage. Structural basis of UV DNA-damage recognition by the DDB1-DDB2 complex.,Scrima A, Konickova R, Czyzewski BK, Kawasaki Y, Jeffrey PD, Groisman R, Nakatani Y, Iwai S, Pavletich NP, Thoma NH Cell. 2008 Dec 26;135(7):1213-23. PMID:19109893[17] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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