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| <StructureSection load='6cfi' size='340' side='right'caption='[[6cfi]], [[Resolution|resolution]] 3.36Å' scene=''> | | <StructureSection load='6cfi' size='340' side='right'caption='[[6cfi]], [[Resolution|resolution]] 3.36Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
| <table><tr><td colspan='2'>[[6cfi]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Baker's_yeast Baker's yeast]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6CFI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6CFI FirstGlance]. <br> | | <table><tr><td colspan='2'>[[6cfi]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae_S288C Saccharomyces cerevisiae S288C] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6CFI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6CFI FirstGlance]. <br> |
| </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=T64:(6-4)PHOTOPRODUCT'>T64</scene></td></tr> | | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.3624191Å</td></tr> |
| <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">RAD4, YER162C ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=559292 Baker's yeast]), RAD23, YEL037C, SYGP-ORF29 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=559292 Baker's yeast])</td></tr> | | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=T64:(6-4)PHOTOPRODUCT'>T64</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=6cfi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cfi OCA], [https://pdbe.org/6cfi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6cfi RCSB], [https://www.ebi.ac.uk/pdbsum/6cfi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6cfi ProSAT]</span></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=6cfi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cfi OCA], [https://pdbe.org/6cfi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6cfi RCSB], [https://www.ebi.ac.uk/pdbsum/6cfi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6cfi ProSAT]</span></td></tr> |
| </table> | | </table> |
| == Function == | | == Function == |
| [[https://www.uniprot.org/uniprot/RAD4_YEAST RAD4_YEAST]] Involved in nucleotide excision repair of DNA damaged with UV light, bulky adducts, or cross-linking agents. [[https://www.uniprot.org/uniprot/RAD23_YEAST RAD23_YEAST]] Plays a central role both in proteasomal degradation of misfolded proteins and DNA repair. Central component of a complex required to couple deglycosylation and proteasome-mediated degradation of misfolded proteins in the endoplasmic reticulum that are retrotranslocated in the cytosol. Involved in DNA excision repair. May play a part in DNA damage recognition and/or in altering chromatin structure to allow access by damage-processing enzymes.
| | [https://www.uniprot.org/uniprot/RAD4_YEAST RAD4_YEAST] Involved in nucleotide excision repair of DNA damaged with UV light, bulky adducts, or cross-linking agents. |
| <div style="background-color:#fffaf0;">
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| == Publication Abstract from PubMed ==
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| Failure in repairing ultraviolet radiation-induced DNA damage can lead to mutations and cancer. Among UV-lesions, the pyrimidine-pyrimidone (6-4) photoproduct (6-4PP) is removed from the genome much faster than the cyclobutane pyrimidine dimer (CPD), owing to the more efficient recognition of 6-4PP by XPC-RAD23B, a key initiator of global-genome nucleotide excision repair (NER). Here, we report a crystal structure of a Rad4-Rad23 (yeast XPC-Rad23B ortholog) bound to 6-4PP-containing DNA and 4-mus molecular dynamics (MD) simulations examining the initial binding of Rad4 to 6-4PP or CPD. This first structure of Rad4/XPC bound to a physiological substrate with matched DNA sequence shows that Rad4 flips out both 6-4PP-containing nucleotide pairs, forming an 'open' conformation. The MD trajectories detail how Rad4/XPC initiates 'opening' 6-4PP: Rad4 initially engages BHD2 to bend/untwist DNA from the minor groove, leading to unstacking and extrusion of the 6-4PP:AA nucleotide pairs towards the major groove. The 5' partner adenine first flips out and is captured by a BHD2/3 groove, while the 3' adenine extrudes episodically, facilitating ensuing insertion of the BHD3 beta-hairpin to open DNA as in the crystal structure. However, CPD resists such Rad4-induced structural distortions. Untwisting/bending from the minor groove may be a common way to interrogate DNA in NER.
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| Structure and mechanism of pyrimidine-pyrimidone (6-4) photoproduct recognition by the Rad4/XPC nucleotide excision repair complex.,Paul D, Mu H, Zhao H, Ouerfelli O, Jeffrey PD, Broyde S, Min JH Nucleic Acids Res. 2019 Jul 9;47(12):6015-6028. doi: 10.1093/nar/gkz359. PMID:31106376<ref>PMID:31106376</ref>
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| From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| </div>
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| <div class="pdbe-citations 6cfi" style="background-color:#fffaf0;"></div>
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| ==See Also== | | ==See Also== |
| *[[DNA repair protein Rad4|DNA repair protein Rad4]] | | *[[DNA repair protein Rad4|DNA repair protein Rad4]] |
| *[[UV excision repair protein|UV excision repair protein]] | | *[[UV excision repair protein|UV excision repair protein]] |
| == References ==
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| <references/>
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| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
| [[Category: Baker's yeast]]
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| [[Category: Large Structures]] | | [[Category: Large Structures]] |
| [[Category: Jeffrey, P D]] | | [[Category: Saccharomyces cerevisiae S288C]] |
| [[Category: Min, J]] | | [[Category: Synthetic construct]] |
| [[Category: Dna binding protein-dna complex]] | | [[Category: Jeffrey PD]] |
| [[Category: Dna damage repair]] | | [[Category: Min J]] |
| [[Category: Nucleotide excision repair]]
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| [[Category: Ultraviolet]]
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| [[Category: Xeroderma pigmentosum]]
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| [[Category: Xpc]]
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