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| | <StructureSection load='2i46' size='340' side='right'caption='[[2i46]], [[Resolution|resolution]] 2.70Å' scene=''> | | <StructureSection load='2i46' size='340' side='right'caption='[[2i46]], [[Resolution|resolution]] 2.70Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2i46]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2I46 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2I46 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2i46]] is a 2 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=2I46 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2I46 FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ACD, PIP1, PTOP ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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]] 2.7Å</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=2i46 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2i46 OCA], [https://pdbe.org/2i46 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2i46 RCSB], [https://www.ebi.ac.uk/pdbsum/2i46 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2i46 ProSAT]</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=2i46 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2i46 OCA], [https://pdbe.org/2i46 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2i46 RCSB], [https://www.ebi.ac.uk/pdbsum/2i46 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2i46 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/ACD_HUMAN ACD_HUMAN]] Component of the shelterin complex (telosome) that is involved in the regulation of telomere length and protection. Shelterin associates with arrays of double-stranded TTAGGG repeats added by telomerase and protects chromosome ends; without its protective activity, telomeres are no longer hidden from the DNA damage surveillance and chromosome ends are inappropriately processed by DNA repair pathways. Promotes binding of POT1 to single-stranded telomeric DNA. Modulates the inhibitory effects of POT1 on telomere elongation. The ACD-POT1 heterodimer enhances telomere elongation by increasing telomerase processivity. Plays a role in shelterin complex assembly. May play a role in organogenesis.<ref>PMID:15181449</ref> <ref>PMID:16166375</ref> <ref>PMID:16880378</ref> <ref>PMID:20231318</ref> <ref>PMID:17237768</ref>
| + | [https://www.uniprot.org/uniprot/ACD_HUMAN ACD_HUMAN] Component of the shelterin complex (telosome) that is involved in the regulation of telomere length and protection. Shelterin associates with arrays of double-stranded TTAGGG repeats added by telomerase and protects chromosome ends; without its protective activity, telomeres are no longer hidden from the DNA damage surveillance and chromosome ends are inappropriately processed by DNA repair pathways. Promotes binding of POT1 to single-stranded telomeric DNA. Modulates the inhibitory effects of POT1 on telomere elongation. The ACD-POT1 heterodimer enhances telomere elongation by increasing telomerase processivity. Plays a role in shelterin complex assembly. May play a role in organogenesis.<ref>PMID:15181449</ref> <ref>PMID:16166375</ref> <ref>PMID:16880378</ref> <ref>PMID:20231318</ref> <ref>PMID:17237768</ref> |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | Telomeres were originally defined as chromosome caps that prevent the natural ends of linear chromosomes from undergoing deleterious degradation and fusion events. POT1 (protection of telomeres) protein binds the single-stranded G-rich DNA overhangs at human chromosome ends and suppresses unwanted DNA repair activities. TPP1 is a previously identified binding partner of POT1 that has been proposed to form part of a six-protein shelterin complex at telomeres. Here, the crystal structure of a domain of human TPP1 reveals an oligonucleotide/oligosaccharide-binding fold that is structurally similar to the beta-subunit of the telomere end-binding protein of a ciliated protozoan, suggesting that TPP1 is the missing beta-subunit of human POT1 protein. Telomeric DNA end-binding proteins have generally been found to inhibit rather than stimulate the action of the chromosome end-replicating enzyme, telomerase. In contrast, we find that TPP1 and POT1 form a complex with telomeric DNA that increases the activity and processivity of the human telomerase core enzyme. We propose that POT1-TPP1 switches from inhibiting telomerase access to the telomere, as a component of shelterin, to serving as a processivity factor for telomerase during telomere extension.
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| - | The POT1-TPP1 telomere complex is a telomerase processivity factor.,Wang F, Podell ER, Zaug AJ, Yang Y, Baciu P, Cech TR, Lei M Nature. 2007 Feb 1;445(7127):506-10. Epub 2007 Jan 21. PMID:17237768<ref>PMID:17237768</ref>
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| - | </div>
| + | |
| - | <div class="pdbe-citations 2i46" style="background-color:#fffaf0;"></div>
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| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Baciu, P]] | + | [[Category: Baciu P]] |
| - | [[Category: Cech, T R]] | + | [[Category: Cech TR]] |
| - | [[Category: Else, T]] | + | [[Category: Else T]] |
| - | [[Category: Hammer, G D]] | + | [[Category: Hammer GD]] |
| - | [[Category: Lei, M]] | + | [[Category: Lei M]] |
| - | [[Category: Podell, E R]] | + | [[Category: Podell ER]] |
| - | [[Category: Wang, F]] | + | [[Category: Wang F]] |
| - | [[Category: Yang, Y T]] | + | [[Category: Yang YT]] |
| - | [[Category: Zaug, A J]] | + | [[Category: Zaug AJ]] |
| - | [[Category: Ob fold]]
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| - | [[Category: Pot1 binding]]
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| - | [[Category: Protein binding]]
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| - | [[Category: Tpp1]]
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| Structural highlights
Function
ACD_HUMAN Component of the shelterin complex (telosome) that is involved in the regulation of telomere length and protection. Shelterin associates with arrays of double-stranded TTAGGG repeats added by telomerase and protects chromosome ends; without its protective activity, telomeres are no longer hidden from the DNA damage surveillance and chromosome ends are inappropriately processed by DNA repair pathways. Promotes binding of POT1 to single-stranded telomeric DNA. Modulates the inhibitory effects of POT1 on telomere elongation. The ACD-POT1 heterodimer enhances telomere elongation by increasing telomerase processivity. Plays a role in shelterin complex assembly. May play a role in organogenesis.[1] [2] [3] [4] [5]
References
- ↑ Liu D, Safari A, O'Connor MS, Chan DW, Laegeler A, Qin J, Songyang Z. PTOP interacts with POT1 and regulates its localization to telomeres. Nat Cell Biol. 2004 Jul;6(7):673-80. Epub 2004 Jun 6. PMID:15181449 doi:http://dx.doi.org/10.1038/ncb1142
- ↑ de Lange T. Shelterin: the protein complex that shapes and safeguards human telomeres. Genes Dev. 2005 Sep 15;19(18):2100-10. PMID:16166375 doi:10.1101/gad.1346005
- ↑ O'Connor MS, Safari A, Xin H, Liu D, Songyang Z. A critical role for TPP1 and TIN2 interaction in high-order telomeric complex assembly. Proc Natl Acad Sci U S A. 2006 Aug 8;103(32):11874-9. Epub 2006 Jul 31. PMID:16880378 doi:0605303103
- ↑ Zaug AJ, Podell ER, Nandakumar J, Cech TR. Functional interaction between telomere protein TPP1 and telomerase. Genes Dev. 2010 Mar 15;24(6):613-22. doi: 10.1101/gad.1881810. PMID:20231318 doi:10.1101/gad.1881810
- ↑ Wang F, Podell ER, Zaug AJ, Yang Y, Baciu P, Cech TR, Lei M. The POT1-TPP1 telomere complex is a telomerase processivity factor. Nature. 2007 Feb 1;445(7127):506-10. Epub 2007 Jan 21. PMID:17237768 doi:nature05454
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