4xhu

From Proteopedia

(Difference between revisions)

Revision as of 07:14, 29 May 2019

The complex structure of Timeless_PAB and PARP-1_catalytic domain

Structural highlights

4xhu is a 4 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Related:	4xht, 4xhw
Gene:	PARP1, ADPRT, PPOL (HUMAN), TIMELESS, TIM, TIM1, TIMELESS1 (HUMAN)
Activity:	NAD(+) ADP-ribosyltransferase, with EC number 2.4.2.30
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[PARP1_HUMAN] Involved in the base excision repair (BER) pathway, by catalyzing the poly(ADP-ribosyl)ation of a limited number of acceptor proteins involved in chromatin architecture and in DNA metabolism. This modification follows DNA damages and appears as an obligatory step in a detection/signaling pathway leading to the reparation of DNA strand breaks. Mediates the poly(ADP-ribosyl)ation of APLF and CHFR. Positively regulates the transcription of MTUS1 and negatively regulates the transcription of MTUS2/TIP150. With EEF1A1 and TXK, forms a complex that acts as a T-helper 1 (Th1) cell-specific transcription factor and binds the promoter of IFN-gamma to directly regulate its transcription, and is thus involved importantly in Th1 cytokine production.^[1] ^[2] ^[3] ^[4] [TIM_HUMAN] Plays an important role in the control of DNA replication, maintenance of replication fork stability, maintenance of genome stability throughout normal DNA replication and in the regulation of the circadian clock. Involved in the determination of period length and in the DNA damage-dependent phase advancing of the circadian clock. Negatively regulates CLOCK|NPAS2-ARTNL/BMAL1|ARTNL2/BMAL2-induced transactivation of PER1 possibly via translocation of PER1 into the nucleus. Forms a complex with TIPIN and this complex regulates DNA replication processes under both normal and stress conditions, stabilizes replication forks and influences both CHEK1 phosphorylation and the intra-S phase checkpoint in response to genotoxic stress. Timeless promotes TIPIN nuclear localization. Involved in cell survival after DNA damage or replication stress. May be specifically required for the ATR-CHEK1 pathway in the replication checkpoint induced by hydroxyurea or ultraviolet light. May also play an important role in epithelial cell morphogenesis and formation of branching tubules.^[5] ^[6] ^[7] ^[8]

Publication Abstract from PubMed

Human Timeless helps stabilize replication forks during normal DNA replication and plays a critical role in activation of the S phase checkpoint and proper establishment of sister chromatid cohesion. However, it remains elusive whether Timeless is involved in the repair of damaged DNA. Here, we identify that Timeless physically interacts with PARP-1 independent of poly(ADP-ribosyl)ation. We present high-resolution crystal structures of Timeless PAB (PARP-1-binding domain) in free form and in complex with PARP-1 catalytic domain. Interestingly, Timeless PAB domain specifically recognizes PARP-1, but not PARP-2 or PARP-3. Timeless-PARP-1 interaction does not interfere with PARP-1 enzymatic activity. We demonstrate that rapid and transient accumulation of Timeless at laser-induced DNA damage sites requires PARP-1, but not poly(ADP-ribosyl)ation and that Timeless is co-trapped with PARP-1 at DNA lesions upon PARP inhibition. Furthermore, we show that Timeless and PARP-1 interaction is required for efficient homologous recombination repair.

Timeless Interacts with PARP-1 to Promote Homologous Recombination Repair.,Xie S, Mortusewicz O, Ma HT, Herr P, Poon RR, Helleday T, Qian C Mol Cell. 2015 Sep 2. pii: S1097-2765(15)00589-4. doi:, 10.1016/j.molcel.2015.07.031. PMID:26344098^[9]

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

References

↑ Maruyama T, Nara K, Yoshikawa H, Suzuki N. Txk, a member of the non-receptor tyrosine kinase of the Tec family, forms a complex with poly(ADP-ribose) polymerase 1 and elongation factor 1alpha and regulates interferon-gamma gene transcription in Th1 cells. Clin Exp Immunol. 2007 Jan;147(1):164-75. PMID:17177976 doi:10.1111/j.1365-2249.2006.03249.x
↑ Ahel I, Ahel D, Matsusaka T, Clark AJ, Pines J, Boulton SJ, West SC. Poly(ADP-ribose)-binding zinc finger motifs in DNA repair/checkpoint proteins. Nature. 2008 Jan 3;451(7174):81-5. doi: 10.1038/nature06420. PMID:18172500 doi:10.1038/nature06420
↑ Reinemund J, Seidel K, Steckelings UM, Zaade D, Klare S, Rompe F, Katerbaum M, Schacherl J, Li Y, Menk M, Schefe JH, Goldin-Lang P, Szabo C, Olah G, Unger T, Funke-Kaiser H. Poly(ADP-ribose) polymerase-1 (PARP-1) transcriptionally regulates angiotensin AT2 receptor (AT2R) and AT2R binding protein (ATBP) genes. Biochem Pharmacol. 2009 Jun 15;77(12):1795-805. doi: 10.1016/j.bcp.2009.02.025., Epub 2009 Mar 19. PMID:19344625 doi:10.1016/j.bcp.2009.02.025
↑ Ahel D, Horejsi Z, Wiechens N, Polo SE, Garcia-Wilson E, Ahel I, Flynn H, Skehel M, West SC, Jackson SP, Owen-Hughes T, Boulton SJ. Poly(ADP-ribose)-dependent regulation of DNA repair by the chromatin remodeling enzyme ALC1. Science. 2009 Sep 4;325(5945):1240-3. doi: 10.1126/science.1177321. Epub 2009 Aug, 6. PMID:19661379 doi:10.1126/science.1177321
↑ Gotter AL, Suppa C, Emanuel BS. Mammalian TIMELESS and Tipin are evolutionarily conserved replication fork-associated factors. J Mol Biol. 2007 Feb 9;366(1):36-52. Epub 2006 Nov 3. PMID:17141802 doi:http://dx.doi.org/S0022-2836(06)01525-7
↑ Unsal-Kacmaz K, Chastain PD, Qu PP, Minoo P, Cordeiro-Stone M, Sancar A, Kaufmann WK. The human Tim/Tipin complex coordinates an Intra-S checkpoint response to UV that slows replication fork displacement. Mol Cell Biol. 2007 Apr;27(8):3131-42. Epub 2007 Feb 12. PMID:17296725 doi:http://dx.doi.org/10.1128/MCB.02190-06
↑ Engelen E, Janssens RC, Yagita K, Smits VA, van der Horst GT, Tamanini F. Mammalian TIMELESS is involved in period determination and DNA damage-dependent phase advancing of the circadian clock. PLoS One. 2013;8(2):e56623. doi: 10.1371/journal.pone.0056623. Epub 2013 Feb 13. PMID:23418588 doi:http://dx.doi.org/10.1371/journal.pone.0056623
↑ Sangoram AM, Saez L, Antoch MP, Gekakis N, Staknis D, Whiteley A, Fruechte EM, Vitaterna MH, Shimomura K, King DP, Young MW, Weitz CJ, Takahashi JS. Mammalian circadian autoregulatory loop: a timeless ortholog and mPer1 interact and negatively regulate CLOCK-BMAL1-induced transcription. Neuron. 1998 Nov;21(5):1101-13. PMID:9856465
↑ Xie S, Mortusewicz O, Ma HT, Herr P, Poon RR, Helleday T, Qian C. Timeless Interacts with PARP-1 to Promote Homologous Recombination Repair. Mol Cell. 2015 Sep 2. pii: S1097-2765(15)00589-4. doi:, 10.1016/j.molcel.2015.07.031. PMID:26344098 doi:http://dx.doi.org/10.1016/j.molcel.2015.07.031

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4xhu"

@@ Line 1: / Line 1: @@
 ==The complex structure of Timeless_PAB and PARP-1_catalytic domain==
-<StructureSection load='4xhu' size='340' side='right' caption='[[4xhu]], [[Resolution|resolution]] 2.09&Aring;' scene=''>
+<StructureSection load='4xhu' size='340' side='right'caption='[[4xhu]], [[Resolution|resolution]] 2.09&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4xhu]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4XHU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4XHU FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4xhu]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4XHU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4XHU FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4xht|4xht]], [[4xhw|4xhw]]</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PARP1, ADPRT, PPOL ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), TIMELESS, TIM, TIM1, TIMELESS1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/NAD(+)_ADP-ribosyltransferase NAD(+) ADP-ribosyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.30 2.4.2.30] </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=4xhu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xhu OCA], [http://pdbe.org/4xhu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4xhu RCSB], [http://www.ebi.ac.uk/pdbsum/4xhu PDBsum]</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=4xhu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xhu OCA], [http://pdbe.org/4xhu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4xhu RCSB], [http://www.ebi.ac.uk/pdbsum/4xhu PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4xhu ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 19: / Line 21: @@
 </div>
 <div class="pdbe-citations 4xhu" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Poly (ADP-ribose) polymerase|Poly (ADP-ribose) polymerase]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Qian, C]]
 [[Category: Xie, S]]
 [[Category: Dna damage response]]
 [[Category: Transferase-replication complex]]

4xhu

From Proteopedia

Revision as of 07:14, 29 May 2019

The complex structure of Timeless_PAB and PARP-1_catalytic domain

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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