7k17
From Proteopedia
(Difference between revisions)
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| - | ==== | + | ==Re-refined crystal structure of DNA-dependent protein kinase catalytic subunit complexed with Ku80 C-terminal helix== |
| - | <StructureSection load='7k17' size='340' side='right'caption='[[7k17]]' scene=''> | + | <StructureSection load='7k17' size='340' side='right'caption='[[7k17]], [[Resolution|resolution]] 4.30Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7k17]] is a 4 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=7K17 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7K17 FirstGlance]. <br> |
| - | </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=7k17 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7k17 OCA], [https://pdbe.org/7k17 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7k17 RCSB], [https://www.ebi.ac.uk/pdbsum/7k17 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7k17 ProSAT]</span></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]] 4.3Å</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=7k17 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7k17 OCA], [https://pdbe.org/7k17 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7k17 RCSB], [https://www.ebi.ac.uk/pdbsum/7k17 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7k17 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/XRCC5_HUMAN XRCC5_HUMAN] Single stranded DNA-dependent ATP-dependent helicase. Has a role in chromosome translocation. The DNA helicase II complex binds preferentially to fork-like ends of double-stranded DNA in a cell cycle-dependent manner. It works in the 3'-5' direction. Binding to DNA may be mediated by XRCC6. Involved in DNA non-homologous end joining (NHEJ) required for double-strand break repair and V(D)J recombination. The XRCC5/6 dimer acts as regulatory subunit of the DNA-dependent protein kinase complex DNA-PK by increasing the affinity of the catalytic subunit PRKDC to DNA by 100-fold. The XRCC5/6 dimer is probably involved in stabilizing broken DNA ends and bringing them together. The assembly of the DNA-PK complex to DNA ends is required for the NHEJ ligation step. In association with NAA15, the XRCC5/6 dimer binds to the osteocalcin promoter and activates osteocalcin expression. The XRCC5/6 dimer probably also acts as a 5'-deoxyribose-5-phosphate lyase (5'-dRP lyase), by catalyzing the beta-elimination of the 5' deoxyribose-5-phosphate at an abasic site near double-strand breaks. XRCC5 probably acts as the catalytic subunit of 5'-dRP activity, and allows to 'clean' the termini of abasic sites, a class of nucleotide damage commonly associated with strand breaks, before such broken ends can be joined. The XRCC5/6 dimer together with APEX1 acts as a negative regulator of transcription.<ref>PMID:7957065</ref> <ref>PMID:8621488</ref> <ref>PMID:12145306</ref> <ref>PMID:20383123</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | DNA-dependent protein kinase (DNA-PK), like all phosphatidylinositol 3-kinase-related kinases (PIKKs), is composed of conserved FAT and kinase domains (FATKINs) along with solenoid structures made of HEAT repeats. These kinases are activated in response to cellular stress signals, but the mechanisms governing activation and regulation remain unresolved. For DNA-PK, all existing structures represent inactive states with resolution limited to 4.3 A at best. Here, we report the cryoelectron microscopy (cryo-EM) structures of DNA-PKcs (DNA-PK catalytic subunit) bound to a DNA end or complexed with Ku70/80 and DNA in both inactive and activated forms at resolutions of 3.7 A overall and 3.2 A for FATKINs. These structures reveal the sequential transition of DNA-PK from inactive to activated forms. Most notably, activation of the kinase involves previously unknown stretching and twisting within individual solenoid segments and loosens DNA-end binding. This unprecedented structural plasticity of helical repeats may be a general regulatory mechanism of HEAT-repeat proteins. | ||
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| + | Structure of an activated DNA-PK and its implications for NHEJ.,Chen X, Xu X, Chen Y, Cheung JC, Wang H, Jiang J, de Val N, Fox T, Gellert M, Yang W Mol Cell. 2020 Dec 24. pii: S1097-2765(20)30907-2. doi:, 10.1016/j.molcel.2020.12.015. PMID:33385326<ref>PMID:33385326</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7k17" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: | + | [[Category: Chen X]] |
| + | [[Category: Gellert M]] | ||
| + | [[Category: Yang W]] | ||
Current revision
Re-refined crystal structure of DNA-dependent protein kinase catalytic subunit complexed with Ku80 C-terminal helix
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