|
|
| (One intermediate revision not shown.) |
| Line 1: |
Line 1: |
| | | | |
| | ==Crystal structure of the N-terminal domain of human Timeless== | | ==Crystal structure of the N-terminal domain of human Timeless== |
| - | <StructureSection load='5mqi' size='340' side='right' caption='[[5mqi]], [[Resolution|resolution]] 1.85Å' scene=''> | + | <StructureSection load='5mqi' size='340' side='right'caption='[[5mqi]], [[Resolution|resolution]] 1.85Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5mqi]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5MQI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5MQI FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5mqi]] is a 1 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=5MQI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5MQI FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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]] 1.847Å</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=5mqi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mqi OCA], [http://pdbe.org/5mqi PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5mqi RCSB], [http://www.ebi.ac.uk/pdbsum/5mqi PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5mqi ProSAT]</span></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=5mqi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mqi OCA], [https://pdbe.org/5mqi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5mqi RCSB], [https://www.ebi.ac.uk/pdbsum/5mqi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5mqi ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/TIM_HUMAN 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.<ref>PMID:17141802</ref> <ref>PMID:17296725</ref> <ref>PMID:23418588</ref> <ref>PMID:9856465</ref> | + | [https://www.uniprot.org/uniprot/TIM_HUMAN 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.<ref>PMID:17141802</ref> <ref>PMID:17296725</ref> <ref>PMID:23418588</ref> <ref>PMID:9856465</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 18: |
Line 19: |
| | </div> | | </div> |
| | <div class="pdbe-citations 5mqi" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 5mqi" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Deoxycytidine kinase 3D structures|Deoxycytidine kinase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Holzer, S]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Kilkenny, M L]] | + | [[Category: Large Structures]] |
| - | [[Category: Pellegrini, L]] | + | [[Category: Holzer S]] |
| - | [[Category: Dna replication]] | + | [[Category: Kilkenny ML]] |
| - | [[Category: Genomic stability]] | + | [[Category: Pellegrini L]] |
| - | [[Category: Replication]]
| + | |
| Structural highlights
Function
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.[1] [2] [3] [4]
Publication Abstract from PubMed
Human Timeless is involved in replication fork stabilization, S-phase checkpoint activation and establishment of sister chromatid cohesion. In the cell, Timeless forms a constitutive heterodimeric complex with Tipin. Here we present the 1.85 A crystal structure of a large N-terminal segment of human Timeless, spanning amino acids 1-463, and we show that this region of human Timeless harbours a partial binding site for Tipin. Furthermore, we identify minimal regions of the two proteins that are required for the formation of a stable Timeless-Tipin complex and provide evidence that the Timeless-Tipin interaction is based on a composite binding interface comprising different domains of Timeless.
Crystal structure of the N-terminal domain of human Timeless and its interaction with Tipin.,Holzer S, Degliesposti G, Kilkenny ML, Maslen SL, Matak-Vinkovic D, Skehel M, Pellegrini L Nucleic Acids Res. 2017 Feb 25. doi: 10.1093/nar/gkx139. PMID:28334766[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ 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
- ↑ Holzer S, Degliesposti G, Kilkenny ML, Maslen SL, Matak-Vinkovic D, Skehel M, Pellegrini L. Crystal structure of the N-terminal domain of human Timeless and its interaction with Tipin. Nucleic Acids Res. 2017 Feb 25. doi: 10.1093/nar/gkx139. PMID:28334766 doi:http://dx.doi.org/10.1093/nar/gkx139
|
