6cfi
From Proteopedia
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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 [ | + | <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> |
</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='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> | ||
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">RAD4, YER162C ([ | + | <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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | <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. |
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | 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. | ||
| + | |||
| + | 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> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6cfi" style="background-color:#fffaf0;"></div> | ||
==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]] | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Revision as of 09:23, 26 May 2021
Crystal structure of Rad4-Rad23 bound to a 6-4 photoproduct UV lesion
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