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5w1r

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Cryo-EM structure of DNAPKcs

5w1r, resolution 4.40Å

Structural highlights

5w1r is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Activity:	Non-specific serine/threonine protein kinase, with EC number 2.7.11.1
Experimental data:	Check to display Experimental Data
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[PRKDC_HUMAN] Severe combined immunodeficiency due to DNA-PKcs deficiency. The disease is caused by mutations affecting the gene represented in this entry.

Function

[PRKDC_HUMAN] Serine/threonine-protein kinase that acts as a molecular sensor for DNA damage. Involved in DNA non-homologous end joining (NHEJ) required for double-strand break (DSB) repair and V(D)J recombination. Must be bound to DNA to express its catalytic properties. Promotes processing of hairpin DNA structures in V(D)J recombination by activation of the hairpin endonuclease artemis (DCLRE1C). The assembly of the DNA-PK complex at DNA ends is also required for the NHEJ ligation step. Required to protect and align broken ends of DNA. May also act as a scaffold protein to aid the localization of DNA repair proteins to the site of damage. Found at the ends of chromosomes, suggesting a further role in the maintenance of telomeric stability and the prevention of chromosomal end fusion. Also involved in modulation of transcription. Recognizes the substrate consensus sequence [ST]-Q. Phosphorylates 'Ser-139' of histone variant H2AX/H2AFX, thereby regulating DNA damage response mechanism. Phosphorylates DCLRE1C, c-Abl/ABL1, histone H1, HSPCA, c-jun/JUN, p53/TP53, PARP1, POU2F1, DHX9, SRF, XRCC1, XRCC1, XRCC4, XRCC5, XRCC6, WRN, MYC and RFA2. Can phosphorylate C1D not only in the presence of linear DNA but also in the presence of supercoiled DNA. Ability to phosphorylate p53/TP53 in the presence of supercoiled DNA is dependent on C1D. Contributes to the determination of the circadian period length by antagonizing phosphorylation of CRY1 'Ser-588' and increasing CRY1 protein stability, most likely through an indirect machanism. Interacts with CRY1 and CRY2; negatively regulates CRY1 phosphorylation.^[1] ^[2] ^[3] ^[4]

Publication Abstract from PubMed

DNA-dependent protein kinase (DNA-PK) is a large protein complex central to the nonhomologous end joining (NHEJ) DNA-repair pathway. It comprises the DNA-PK catalytic subunit (DNA-PKcs) and the heterodimer of DNA-binding proteins Ku70 and Ku80. Here, we report the cryo-electron microscopy (cryo-EM) structures of human DNA-PKcs at 4.4-A resolution and the DNA-PK holoenzyme at 5.8-A resolution. The DNA-PKcs structure contains three distinct segments: the N-terminal region with an arm and a bridge, the circular cradle, and the head that includes the kinase domain. Two perpendicular apertures exist in the structure, which are sufficiently large for the passage of dsDNA. The DNA-PK holoenzyme cryo-EM map reveals density for the C-terminal globular domain of Ku80 that interacts with the arm of DNA-PKcs. The Ku80-binding site is adjacent to the previously identified density for the DNA-binding region of the Ku70/Ku80 complex, suggesting concerted DNA interaction by DNA-PKcs and the Ku complex.

Cryo-EM structure of the DNA-PK holoenzyme.,Sharif H, Li Y, Dong Y, Dong L, Wang WL, Mao Y, Wu H Proc Natl Acad Sci U S A. 2017 Jul 11;114(28):7367-7372. doi:, 10.1073/pnas.1707386114. Epub 2017 Jun 26. PMID:28652322^[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Soubeyrand S, Pope L, Pakuts B, Hache RJ. Threonines 2638/2647 in DNA-PK are essential for cellular resistance to ionizing radiation. Cancer Res. 2003 Mar 15;63(6):1198-201. PMID:12649176
↑ Wechsler T, Chen BP, Harper R, Morotomi-Yano K, Huang BC, Meek K, Cleaver JE, Chen DJ, Wabl M. DNA-PKcs function regulated specifically by protein phosphatase 5. Proc Natl Acad Sci U S A. 2004 Feb 3;101(5):1247-52. Epub 2004 Jan 20. PMID:14734805 doi:http://dx.doi.org/10.1073/pnas.0307765100
↑ Ma Y, Lu H, Tippin B, Goodman MF, Shimazaki N, Koiwai O, Hsieh CL, Schwarz K, Lieber MR. A biochemically defined system for mammalian nonhomologous DNA end joining. Mol Cell. 2004 Dec 3;16(5):701-13. PMID:15574326 doi:10.1016/j.molcel.2004.11.017
↑ Yavuzer U, Smith GC, Bliss T, Werner D, Jackson SP. DNA end-independent activation of DNA-PK mediated via association with the DNA-binding protein C1D. Genes Dev. 1998 Jul 15;12(14):2188-99. PMID:9679063
↑ Sharif H, Li Y, Dong Y, Dong L, Wang WL, Mao Y, Wu H. Cryo-EM structure of the DNA-PK holoenzyme. Proc Natl Acad Sci U S A. 2017 Jul 11;114(28):7367-7372. doi:, 10.1073/pnas.1707386114. Epub 2017 Jun 26. PMID:28652322 doi:http://dx.doi.org/10.1073/pnas.1707386114

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5w1r"

@@ Line 3: / Line 3: @@
 <SX load='5w1r' size='340' side='right' viewer='molstar' caption='[[5w1r]], [[Resolution|resolution]] 4.40&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5w1r]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5W1R OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5W1R FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5w1r]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5W1R OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5W1R FirstGlance]. <br>
 </td></tr><tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </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=5w1r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5w1r OCA], [http://pdbe.org/5w1r PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5w1r RCSB], [http://www.ebi.ac.uk/pdbsum/5w1r PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5w1r ProSAT]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5w1r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5w1r OCA], [http://pdbe.org/5w1r PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5w1r RCSB], [http://www.ebi.ac.uk/pdbsum/5w1r PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5w1r ProSAT]</span></td></tr>
 </table>
 == Disease ==

5w1r

From Proteopedia

Current revision

Cryo-EM structure of DNAPKcs

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

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