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- | [[Image:1xjv.gif|left|200px]] | |
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- | {{Structure
| + | ==Crystal structure of human POT1 bound to telomeric single-stranded DNA (TTAGGGTTAG)== |
- | |PDB= 1xjv |SIZE=350|CAPTION= <scene name='initialview01'>1xjv</scene>, resolution 1.73Å
| + | <StructureSection load='1xjv' size='340' side='right'caption='[[1xjv]], [[Resolution|resolution]] 1.73Å' scene=''> |
- | |SITE=
| + | == Structural highlights == |
- | |LIGAND=
| + | <table><tr><td colspan='2'>[[1xjv]] 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=1XJV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1XJV FirstGlance]. <br> |
- | |ACTIVITY=
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.73Å</td></tr> |
- | |GENE= POT1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1xjv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1xjv OCA], [https://pdbe.org/1xjv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1xjv RCSB], [https://www.ebi.ac.uk/pdbsum/1xjv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1xjv ProSAT]</span></td></tr> |
- | }}
| + | </table> |
- | | + | == Function == |
- | '''Crystal structure of human POT1 bound to telomeric single-stranded DNA (TTAGGGTTAG)''' | + | [https://www.uniprot.org/uniprot/POTE1_HUMAN POTE1_HUMAN] Component of the telomerase ribonucleoprotein (RNP) complex that is essential for the replication of chromosome termini. Is a component of the double-stranded telomeric DNA-binding TRF1 complex which is involved in the regulation of telomere length by cis-inhibition of telomerase. Also acts as a single-stranded telomeric DNA-binding protein and thus may act as a downstream effector of the TRF1 complex and may transduce information about telomere maintenance and/or length to the telomere terminus. 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. Binds to two or more telomeric single-stranded 5'-TTAGGG-3' repeats (G-strand) and with high specificity to a minimal telomeric single-stranded 5'-TAGGGTTAG-3' sequence. Binds telomeric single-stranded sequences internally or at proximity of a 3'-end. Its activity is TERT dependent but it does not increase TERT activity by itself. In contrast, the ACD-POT1 heterodimer enhances telomere elongation by increasing telomerase processivity.<ref>PMID:12781132</ref> <ref>PMID:12768206</ref> <ref>PMID:16166375</ref> <ref>PMID:17237768</ref> <ref>PMID:20231318</ref> |
- | | + | == Evolutionary Conservation == |
- | | + | [[Image:Consurf_key_small.gif|200px|right]] |
- | ==Overview== | + | Check<jmol> |
- | The POT1 (protection of telomeres 1) protein binds the single-stranded overhang at the ends of chromosomes in diverse eukaryotes. It is essential for chromosome end-protection in the fission yeast Schizosaccharomyces pombe, and it is involved in regulation of telomere length in human cells. Here, we report the crystal structure at a resolution of 1.73 A of the N-terminal half of human POT1 (hPOT1) protein bound to a telomeric single-stranded DNA (ssDNA) decamer, TTAGGGTTAG, the minimum tight-binding sequence indicated by in vitro binding assays. The structure reveals that hPOT1 contains two oligonucleotide/ oligosaccharide-binding (OB) folds; the N-terminal OB fold binds the first six nucleotides, resembling the structure of the S. pombe Pot1pN-ssDNA complex, whereas the second OB fold binds and protects the 3' end of the ssDNA. These results provide an atomic-resolution model for chromosome end-capping.
| + | <jmolCheckbox> |
- | | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/xj/1xjv_consurf.spt"</scriptWhenChecked> |
- | ==About this Structure== | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
- | 1XJV is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1XJV OCA].
| + | <text>to colour the structure by Evolutionary Conservation</text> |
- | | + | </jmolCheckbox> |
- | ==Reference== | + | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1xjv ConSurf]. |
- | Structure of human POT1 bound to telomeric single-stranded DNA provides a model for chromosome end-protection., Lei M, Podell ER, Cech TR, Nat Struct Mol Biol. 2004 Dec;11(12):1223-9. Epub 2004 Nov 21. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15558049 15558049]
| + | <div style="clear:both"></div> |
| + | == References == |
| + | <references/> |
| + | __TOC__ |
| + | </StructureSection> |
| [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
- | [[Category: Single protein]] | + | [[Category: Large Structures]] |
- | [[Category: Cech, T R.]] | + | [[Category: Cech TR]] |
- | [[Category: Lei, M.]] | + | [[Category: Lei M]] |
- | [[Category: Podell, E R.]] | + | [[Category: Podell ER]] |
- | [[Category: telomere; protein-dna complex; single-stranded dna]]
| + | |
- | | + | |
- | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 15:10:45 2008''
| + | |
| Structural highlights
Function
POTE1_HUMAN Component of the telomerase ribonucleoprotein (RNP) complex that is essential for the replication of chromosome termini. Is a component of the double-stranded telomeric DNA-binding TRF1 complex which is involved in the regulation of telomere length by cis-inhibition of telomerase. Also acts as a single-stranded telomeric DNA-binding protein and thus may act as a downstream effector of the TRF1 complex and may transduce information about telomere maintenance and/or length to the telomere terminus. 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. Binds to two or more telomeric single-stranded 5'-TTAGGG-3' repeats (G-strand) and with high specificity to a minimal telomeric single-stranded 5'-TAGGGTTAG-3' sequence. Binds telomeric single-stranded sequences internally or at proximity of a 3'-end. Its activity is TERT dependent but it does not increase TERT activity by itself. In contrast, the ACD-POT1 heterodimer enhances telomere elongation by increasing telomerase processivity.[1] [2] [3] [4] [5]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
References
- ↑ Colgin LM, Baran K, Baumann P, Cech TR, Reddel RR. Human POT1 facilitates telomere elongation by telomerase. Curr Biol. 2003 May 27;13(11):942-6. PMID:12781132
- ↑ Loayza D, De Lange T. POT1 as a terminal transducer of TRF1 telomere length control. Nature. 2003 Jun 26;423(6943):1013-8. Epub 2003 May 25. PMID:12768206 doi:10.1038/nature01688
- ↑ 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
- ↑ 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
- ↑ 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
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