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| | ==Crystal structure of HIRAN domain of human HLTF in complex with DNA== | | ==Crystal structure of HIRAN domain of human HLTF in complex with DNA== |
| - | <StructureSection load='4xzf' size='340' side='right' caption='[[4xzf]], [[Resolution|resolution]] 1.38Å' scene=''> | + | <StructureSection load='4xzf' size='340' side='right'caption='[[4xzf]], [[Resolution|resolution]] 1.38Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4xzf]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4XZF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4XZF FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4xzf]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4XZF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4XZF FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4xzg|4xzg]]</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]] 1.38Å</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=4xzf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xzf OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4xzf RCSB], [http://www.ebi.ac.uk/pdbsum/4xzf PDBsum]</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=4xzf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xzf OCA], [https://pdbe.org/4xzf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4xzf RCSB], [https://www.ebi.ac.uk/pdbsum/4xzf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4xzf ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/HLTF_HUMAN HLTF_HUMAN]] Has both helicase and E3 ubiquitin ligase activities. Possesses intrinsic ATP-dependent nucleosome-remodeling activity; This activity may be required for transcriptional activation or repression of specific target promoters (By similarity). These may include the SERPINE1 and HIV-1 promoters and the SV40 enhancer, to which this protein can bind directly. Plays a role in error-free postreplication repair (PRR) of damaged DNA and maintains genomic stability through acting as a ubiquitin ligase for 'Lys-63'-linked polyubiquitination of chromatin-bound PCNA.<ref>PMID:10391891</ref> <ref>PMID:18316726</ref> <ref>PMID:18719106</ref> <ref>PMID:7876228</ref> <ref>PMID:8672239</ref> <ref>PMID:9126292</ref> | + | [https://www.uniprot.org/uniprot/HLTF_HUMAN HLTF_HUMAN] Has both helicase and E3 ubiquitin ligase activities. Possesses intrinsic ATP-dependent nucleosome-remodeling activity; This activity may be required for transcriptional activation or repression of specific target promoters (By similarity). These may include the SERPINE1 and HIV-1 promoters and the SV40 enhancer, to which this protein can bind directly. Plays a role in error-free postreplication repair (PRR) of damaged DNA and maintains genomic stability through acting as a ubiquitin ligase for 'Lys-63'-linked polyubiquitination of chromatin-bound PCNA.<ref>PMID:10391891</ref> <ref>PMID:18316726</ref> <ref>PMID:18719106</ref> <ref>PMID:7876228</ref> <ref>PMID:8672239</ref> <ref>PMID:9126292</ref> |
| - | <div style="background-color:#fffaf0;">
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| - | == Publication Abstract from PubMed ==
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| - | HLTF (helicase-like transcription factor) is a yeast RAD5 homolog found in mammals. HLTF has E3 ubiquitin ligase and DNA helicase activities, and plays a pivotal role in the template-switching (TS) pathway of DNA damage tolerance. HLTF has an N-terminal domain that has been designated the HIRAN (HIP116 and RAD5 N-terminal) domain. The HIRAN domain has been hypothesized to play a role in DNA-binding; however, the structural basis of, and functional evidence for, the HIRAN domain in DNA-binding has remained unclear. Here we show for the first time the crystal structure of the HIRAN domain of human HLTF in complex with DNA. The HIRAN domain is composed of six beta-strands and two alpha-helices, forming an OB-fold structure frequently found in ssDNA-binding proteins, including in RPA (replication factor A). Interestingly, this study reveals that the HIRAN domain interacts with not only a single-stranded DNA but also a duplex DNA. Furthermore, the structure unexpectedly clarifies that the HIRAN domain specifically recognizes the 3'-end of DNA. These results suggest that the HIRAN domain functions as a sensor to the 3'-end of the primer strand at the stalled replication fork and that the domain facilitates fork regression. HLTF is recruited to a damaged site through the HIRAN domain at the stalled replication fork. Furthermore, our results have implications for the mechanism of TS.
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| - | Structure of a Novel DNA-binding Domain of Helicase-like Transcription Factor (HLTF) and Its Functional Implication in DNA Damage Tolerance.,Hishiki A, Hara K, Ikegaya Y, Yokoyama H, Shimizu T, Sato M, Hashimoto H J Biol Chem. 2015 Apr 9. pii: jbc.M115.643643. PMID:25858588<ref>PMID:25858588</ref>
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| - | </div>
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| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Hashimoto, H]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Hishiki, A]] | + | [[Category: Large Structures]] |
| - | [[Category: Dna binding protein-dna complex]] | + | [[Category: Synthetic construct]] |
| - | [[Category: Dna repair]] | + | [[Category: Hashimoto H]] |
| | + | [[Category: Hishiki A]] |
| Structural highlights
Function
HLTF_HUMAN Has both helicase and E3 ubiquitin ligase activities. Possesses intrinsic ATP-dependent nucleosome-remodeling activity; This activity may be required for transcriptional activation or repression of specific target promoters (By similarity). These may include the SERPINE1 and HIV-1 promoters and the SV40 enhancer, to which this protein can bind directly. Plays a role in error-free postreplication repair (PRR) of damaged DNA and maintains genomic stability through acting as a ubiquitin ligase for 'Lys-63'-linked polyubiquitination of chromatin-bound PCNA.[1] [2] [3] [4] [5] [6]
References
- ↑ Ding H, Benotmane AM, Suske G, Collen D, Belayew A. Functional interactions between Sp1 or Sp3 and the helicase-like transcription factor mediate basal expression from the human plasminogen activator inhibitor-1 gene. J Biol Chem. 1999 Jul 9;274(28):19573-80. PMID:10391891
- ↑ Unk I, Hajdu I, Fatyol K, Hurwitz J, Yoon JH, Prakash L, Prakash S, Haracska L. Human HLTF functions as a ubiquitin ligase for proliferating cell nuclear antigen polyubiquitination. Proc Natl Acad Sci U S A. 2008 Mar 11;105(10):3768-73. doi:, 10.1073/pnas.0800563105. Epub 2008 Mar 3. PMID:18316726 doi:http://dx.doi.org/10.1073/pnas.0800563105
- ↑ Motegi A, Liaw HJ, Lee KY, Roest HP, Maas A, Wu X, Moinova H, Markowitz SD, Ding H, Hoeijmakers JH, Myung K. Polyubiquitination of proliferating cell nuclear antigen by HLTF and SHPRH prevents genomic instability from stalled replication forks. Proc Natl Acad Sci U S A. 2008 Aug 26;105(34):12411-6. Epub 2008 Aug 21. PMID:18719106 doi:0805685105
- ↑ Sheridan PL, Schorpp M, Voz ML, Jones KA. Cloning of an SNF2/SWI2-related protein that binds specifically to the SPH motifs of the SV40 enhancer and to the HIV-1 promoter. J Biol Chem. 1995 Mar 3;270(9):4575-87. PMID:7876228
- ↑ Ding H, Descheemaeker K, Marynen P, Nelles L, Carvalho T, Carmo-Fonseca M, Collen D, Belayew A. Characterization of a helicase-like transcription factor involved in the expression of the human plasminogen activator inhibitor-1 gene. DNA Cell Biol. 1996 Jun;15(6):429-42. PMID:8672239
- ↑ Gong X, Kaushal S, Ceccarelli E, Bogdanova N, Neville C, Nguyen T, Clark H, Khatib ZA, Valentine M, Look AT, Rosenthal N. Developmental regulation of Zbu1, a DNA-binding member of the SWI2/SNF2 family. Dev Biol. 1997 Mar 15;183(2):166-82. PMID:9126292 doi:http://dx.doi.org/10.1006/dbio.1996.8486
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