7zyg
From Proteopedia
(Difference between revisions)
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[7zyg]] is a 6 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=7ZYG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7ZYG FirstGlance]. <br> | <table><tr><td colspan='2'>[[7zyg]] is a 6 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=7ZYG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7ZYG FirstGlance]. <br> | ||
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.68Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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=7zyg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7zyg OCA], [https://pdbe.org/7zyg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7zyg RCSB], [https://www.ebi.ac.uk/pdbsum/7zyg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7zyg 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=7zyg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7zyg OCA], [https://pdbe.org/7zyg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7zyg RCSB], [https://www.ebi.ac.uk/pdbsum/7zyg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7zyg ProSAT]</span></td></tr> | ||
</table> | </table> | ||
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Nonhomologous end joining is a critical mechanism that repairs DNA double-strand breaks in human cells. In this work, we address the structural and functional role of the accessory protein PAXX [paralog of x-ray repair cross-complementing protein 4 (XRCC4) and XRCC4-like factor (XLF)] in this mechanism. Here, we report high-resolution cryo-electron microscopy (cryo-EM) and x-ray crystallography structures of the PAXX C-terminal Ku-binding motif bound to Ku70/80 and cryo-EM structures of PAXX bound to two alternate DNA-dependent protein kinase (DNA-PK) end-bridging dimers, mediated by either Ku80 or XLF. We identify residues critical for the Ku70/PAXX interaction in vitro and in cells. We demonstrate that PAXX and XLF can bind simultaneously to the Ku heterodimer and act as structural bridges in alternate forms of DNA-PK dimers. Last, we show that engagement of both proteins provides a complementary advantage for DNA end synapsis and end joining in cells. | Nonhomologous end joining is a critical mechanism that repairs DNA double-strand breaks in human cells. In this work, we address the structural and functional role of the accessory protein PAXX [paralog of x-ray repair cross-complementing protein 4 (XRCC4) and XRCC4-like factor (XLF)] in this mechanism. Here, we report high-resolution cryo-electron microscopy (cryo-EM) and x-ray crystallography structures of the PAXX C-terminal Ku-binding motif bound to Ku70/80 and cryo-EM structures of PAXX bound to two alternate DNA-dependent protein kinase (DNA-PK) end-bridging dimers, mediated by either Ku80 or XLF. We identify residues critical for the Ku70/PAXX interaction in vitro and in cells. We demonstrate that PAXX and XLF can bind simultaneously to the Ku heterodimer and act as structural bridges in alternate forms of DNA-PK dimers. Last, we show that engagement of both proteins provides a complementary advantage for DNA end synapsis and end joining in cells. | ||
| - | PAXX binding to the NHEJ machinery explains functional redundancy with XLF.,Seif-El-Dahan M, Kefala-Stavridi A, Frit P, Hardwick SW, Chirgadze DY, Maia De Oliviera T, Britton S, Barboule N, Bossaert M, Pandurangan AP, Meek K, Blundell TL, Ropars V, Calsou P, Charbonnier JB, Chaplin AK Sci Adv. 2023 Jun 2;9(22):eadg2834. doi: 10.1126/sciadv.adg2834. Epub 2023 May , 31. PMID:37256950<ref>PMID:37256950</ref> | + | PAXX binding to the NHEJ machinery explains functional redundancy with XLF.,Seif-El-Dahan M, Kefala-Stavridi A, Frit P, Hardwick SW, Chirgadze DY, Maia De Oliviera T, Andreani J, Britton S, Barboule N, Bossaert M, Pandurangan AP, Meek K, Blundell TL, Ropars V, Calsou P, Charbonnier JB, Chaplin AK Sci Adv. 2023 Jun 2;9(22):eadg2834. doi: 10.1126/sciadv.adg2834. Epub 2023 May , 31. PMID:37256950<ref>PMID:37256950</ref> |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
Current revision
CryoEM structure of Ku heterodimer bound to DNA, PAXX and XLF
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