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| - | [[Image:1jjr.gif|left|200px]]<br /> | |
| - | <applet load="1jjr" size="450" color="white" frame="true" align="right" spinBox="true" | |
| - | caption="1jjr" /> | |
| - | '''The Three-Dimensional Structure of the C-terminal DNA Binding Domain of Human Ku70'''<br /> | |
| | | | |
| - | ==Overview== | + | ==The Three-Dimensional Structure of the C-terminal DNA Binding Domain of Human Ku70== |
| - | The proteins Ku70 (69.8 kDa) and Ku80 (82.7 kDa) form a heterodimeric, complex that is an essential component of the nonhomologous end joining, DNA double-strand break repair pathway in mammalian cells. Interaction of, Ku with DNA is central for the functions of Ku. Ku70, which is mainly, responsible for the DNA binding activity of the Ku heterodimer, contains, two DNA-binding domains. We have solved the solution structure of the, Ku80-independent DNA-binding domain of Ku70 encompassing residues 536-609, using nuclear magnetic resonance spectroscopy. Residues 536-560 are highly, flexible and have a random structure but form specific interactions with, DNA. Residues 561-609 of Ku70 form a well defined structure with 3, alpha-helices and also interact with DNA. The three-dimensional structure, indicates that all conserved hydrophobic residues are in the hydrophobic, core and therefore may be important for structural integrity. Most of the, conserved positively charged residues are likely to be critical for DNA, recognition. The C-terminal DNA-binding domain of Ku70 contains a, helix-extended strand-helix motif, which occurs in other nucleic, acid-binding proteins and may represent a common nucleic acid binding, motif. | + | <StructureSection load='1jjr' size='340' side='right'caption='[[1jjr]]' scene=''> |
| | + | == Structural highlights == |
| | + | <table><tr><td colspan='2'>[[1jjr]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1JJR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1JJR FirstGlance]. <br> |
| | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=1jjr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1jjr OCA], [https://pdbe.org/1jjr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1jjr RCSB], [https://www.ebi.ac.uk/pdbsum/1jjr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1jjr ProSAT]</span></td></tr> |
| | + | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/XRCC6_HUMAN XRCC6_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. Required for osteocalcin gene expression. 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. 5'-dRP lyase activity 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:2466842</ref> <ref>PMID:8621488</ref> <ref>PMID:7957065</ref> <ref>PMID:9742108</ref> <ref>PMID:12145306</ref> <ref>PMID:20493174</ref> <ref>PMID:20383123</ref> |
| | + | <div style="background-color:#fffaf0;"> |
| | + | == Publication Abstract from PubMed == |
| | + | The proteins Ku70 (69.8 kDa) and Ku80 (82.7 kDa) form a heterodimeric complex that is an essential component of the nonhomologous end joining DNA double-strand break repair pathway in mammalian cells. Interaction of Ku with DNA is central for the functions of Ku. Ku70, which is mainly responsible for the DNA binding activity of the Ku heterodimer, contains two DNA-binding domains. We have solved the solution structure of the Ku80-independent DNA-binding domain of Ku70 encompassing residues 536-609 using nuclear magnetic resonance spectroscopy. Residues 536-560 are highly flexible and have a random structure but form specific interactions with DNA. Residues 561-609 of Ku70 form a well defined structure with 3 alpha-helices and also interact with DNA. The three-dimensional structure indicates that all conserved hydrophobic residues are in the hydrophobic core and therefore may be important for structural integrity. Most of the conserved positively charged residues are likely to be critical for DNA recognition. The C-terminal DNA-binding domain of Ku70 contains a helix-extended strand-helix motif, which occurs in other nucleic acid-binding proteins and may represent a common nucleic acid binding motif. |
| | | | |
| - | ==About this Structure==
| + | The three-dimensional structure of the C-terminal DNA-binding domain of human Ku70.,Zhang Z, Zhu L, Lin D, Chen F, Chen DJ, Chen Y J Biol Chem. 2001 Oct 12;276(41):38231-6. Epub 2001 Jul 16. PMID:11457852<ref>PMID:11457852</ref> |
| - | 1JJR is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1JJR OCA].
| + | |
| | | | |
| - | ==Reference==
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| - | The three-dimensional structure of the C-terminal DNA-binding domain of human Ku70., Zhang Z, Zhu L, Lin D, Chen F, Chen DJ, Chen Y, J Biol Chem. 2001 Oct 12;276(41):38231-6. Epub 2001 Jul 16. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=11457852 11457852]
| + | </div> |
| - | [[Category: Homo sapiens]]
| + | <div class="pdbe-citations 1jjr" style="background-color:#fffaf0;"></div> |
| - | [[Category: Single protein]]
| + | |
| - | [[Category: Chen, Y.]]
| + | |
| - | [[Category: Zhang, Z.]]
| + | |
| - | [[Category: dna repair protein]]
| + | |
| - | [[Category: ku70]]
| + | |
| - | [[Category: protein-dna interaction]]
| + | |
| - | [[Category: solution structure]]
| + | |
| | | | |
| - | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 17:41:17 2007''
| + | ==See Also== |
| | + | *[[Ku protein|Ku protein]] |
| | + | == References == |
| | + | <references/> |
| | + | __TOC__ |
| | + | </StructureSection> |
| | + | [[Category: Homo sapiens]] |
| | + | [[Category: Large Structures]] |
| | + | [[Category: Chen Y]] |
| | + | [[Category: Zhang Z]] |
| Structural highlights
Function
XRCC6_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. Required for osteocalcin gene expression. 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. 5'-dRP lyase activity 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.[1] [2] [3] [4] [5] [6] [7]
Publication Abstract from PubMed
The proteins Ku70 (69.8 kDa) and Ku80 (82.7 kDa) form a heterodimeric complex that is an essential component of the nonhomologous end joining DNA double-strand break repair pathway in mammalian cells. Interaction of Ku with DNA is central for the functions of Ku. Ku70, which is mainly responsible for the DNA binding activity of the Ku heterodimer, contains two DNA-binding domains. We have solved the solution structure of the Ku80-independent DNA-binding domain of Ku70 encompassing residues 536-609 using nuclear magnetic resonance spectroscopy. Residues 536-560 are highly flexible and have a random structure but form specific interactions with DNA. Residues 561-609 of Ku70 form a well defined structure with 3 alpha-helices and also interact with DNA. The three-dimensional structure indicates that all conserved hydrophobic residues are in the hydrophobic core and therefore may be important for structural integrity. Most of the conserved positively charged residues are likely to be critical for DNA recognition. The C-terminal DNA-binding domain of Ku70 contains a helix-extended strand-helix motif, which occurs in other nucleic acid-binding proteins and may represent a common nucleic acid binding motif.
The three-dimensional structure of the C-terminal DNA-binding domain of human Ku70.,Zhang Z, Zhu L, Lin D, Chen F, Chen DJ, Chen Y J Biol Chem. 2001 Oct 12;276(41):38231-6. Epub 2001 Jul 16. PMID:11457852[8]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Reeves WH, Sthoeger ZM. Molecular cloning of cDNA encoding the p70 (Ku) lupus autoantigen. J Biol Chem. 1989 Mar 25;264(9):5047-52. PMID:2466842
- ↑ Chung U, Igarashi T, Nishishita T, Iwanari H, Iwamatsu A, Suwa A, Mimori T, Hata K, Ebisu S, Ogata E, Fujita T, Okazaki T. The interaction between Ku antigen and REF1 protein mediates negative gene regulation by extracellular calcium. J Biol Chem. 1996 Apr 12;271(15):8593-8. PMID:8621488
- ↑ Tuteja N, Tuteja R, Ochem A, Taneja P, Huang NW, Simoncsits A, Susic S, Rahman K, Marusic L, Chen J, et al.. Human DNA helicase II: a novel DNA unwinding enzyme identified as the Ku autoantigen. EMBO J. 1994 Oct 17;13(20):4991-5001. PMID:7957065
- ↑ West RB, Yaneva M, Lieber MR. Productive and nonproductive complexes of Ku and DNA-dependent protein kinase at DNA termini. Mol Cell Biol. 1998 Oct;18(10):5908-20. PMID:9742108
- ↑ Willis DM, Loewy AP, Charlton-Kachigian N, Shao JS, Ornitz DM, Towler DA. Regulation of osteocalcin gene expression by a novel Ku antigen transcription factor complex. J Biol Chem. 2002 Oct 4;277(40):37280-91. Epub 2002 Jul 26. PMID:12145306 doi:http://dx.doi.org/10.1074/jbc.M206482200
- ↑ Liu H, Herrmann CH, Chiang K, Sung TL, Moon SH, Donehower LA, Rice AP. 55K isoform of CDK9 associates with Ku70 and is involved in DNA repair. Biochem Biophys Res Commun. 2010 Jun 25;397(2):245-50. doi:, 10.1016/j.bbrc.2010.05.092. Epub 2010 May 20. PMID:20493174 doi:10.1016/j.bbrc.2010.05.092
- ↑ Roberts SA, Strande N, Burkhalter MD, Strom C, Havener JM, Hasty P, Ramsden DA. Ku is a 5'-dRP/AP lyase that excises nucleotide damage near broken ends. Nature. 2010 Apr 22;464(7292):1214-7. doi: 10.1038/nature08926. Epub 2010 Apr 11. PMID:20383123 doi:http://dx.doi.org/10.1038/nature08926
- ↑ Zhang Z, Zhu L, Lin D, Chen F, Chen DJ, Chen Y. The three-dimensional structure of the C-terminal DNA-binding domain of human Ku70. J Biol Chem. 2001 Oct 12;276(41):38231-6. Epub 2001 Jul 16. PMID:11457852 doi:http://dx.doi.org/10.1074/jbc.M105238200
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