7s1o

From Proteopedia

(Difference between revisions)

Revision as of 08:44, 23 February 2022

Structure of human POT1C

Structural highlights

7s1o is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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]

Publication Abstract from PubMed

Telomeric POT1-TPP1 binding is critical to telomere maintenance and disruption of this complex may lead to cancer. Current data suggests a reduction of intracellular POT1 levels in the absence of TPP1. Here we provide evidence of POT1 plasticity that contributes to its lack of stability in the absence of TPP1 binding. Structural data reveals inter- and intramolecular POT1C domain flexibility in the absence of TPP1. Thermostability and proteolytic resistance assays show that POT1C and the mutant complex POT1C(Q623H)-TPP1(PBD) are less stable than the wild type POT1C-TPP1(PBD), suggesting that TPP1 binding to POT1 stabilizes POT1C and makes it less accessible to proteasomal degradation in the cell. Disruption of the POT1-TPP1 complex such as through cancer-associated mutations leads to a reduction of intracellular POT1, telomere uncapping, and telomere associated DNA damage response (DDR). DDR in turn leads to senescence or genomic instability and oncogenesis.

POT1-TPP1 binding stabilizes POT1, promoting efficient telomere maintenance.,Aramburu T, Kelich J, Rice C, Skordalakes E Comput Struct Biotechnol J. 2022 Jan 11;20:675-684. doi:, 10.1016/j.csbj.2022.01.005. eCollection 2022. PMID:35140887^[6]

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

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
↑ Aramburu T, Kelich J, Rice C, Skordalakes E. POT1-TPP1 binding stabilizes POT1, promoting efficient telomere maintenance. Comput Struct Biotechnol J. 2022 Jan 11;20:675-684. doi:, 10.1016/j.csbj.2022.01.005. eCollection 2022. PMID:35140887 doi:http://dx.doi.org/10.1016/j.csbj.2022.01.005

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/7s1o"

@@ Line 1: / Line 1: @@
 ==Structure of human POT1C==
-<StructureSection load='7s1o' size='340' side='right'caption='[[7s1o]]' scene=''>
+<StructureSection load='7s1o' size='340' side='right'caption='[[7s1o]], [[Resolution|resolution]] 2.55&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7S1O OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7S1O FirstGlance]. <br>
+<table><tr><td colspan='2'>[[7s1o]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7S1O OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7S1O FirstGlance]. <br>
-</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=7s1o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7s1o OCA], [https://pdbe.org/7s1o PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7s1o RCSB], [https://www.ebi.ac.uk/pdbsum/7s1o PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7s1o ProSAT]</span></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</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=7s1o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7s1o OCA], [https://pdbe.org/7s1o PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7s1o RCSB], [https://www.ebi.ac.uk/pdbsum/7s1o PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7s1o ProSAT]</span></td></tr>
 </table>
+== Function ==
+[[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>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Telomeric POT1-TPP1 binding is critical to telomere maintenance and disruption of this complex may lead to cancer. Current data suggests a reduction of intracellular POT1 levels in the absence of TPP1. Here we provide evidence of POT1 plasticity that contributes to its lack of stability in the absence of TPP1 binding. Structural data reveals inter- and intramolecular POT1C domain flexibility in the absence of TPP1. Thermostability and proteolytic resistance assays show that POT1C and the mutant complex POT1C(Q623H)-TPP1(PBD) are less stable than the wild type POT1C-TPP1(PBD), suggesting that TPP1 binding to POT1 stabilizes POT1C and makes it less accessible to proteasomal degradation in the cell. Disruption of the POT1-TPP1 complex such as through cancer-associated mutations leads to a reduction of intracellular POT1, telomere uncapping, and telomere associated DNA damage response (DDR). DDR in turn leads to senescence or genomic instability and oncogenesis.
+POT1-TPP1 binding stabilizes POT1, promoting efficient telomere maintenance.,Aramburu T, Kelich J, Rice C, Skordalakes E Comput Struct Biotechnol J. 2022 Jan 11;20:675-684. doi:, 10.1016/j.csbj.2022.01.005. eCollection 2022. PMID:35140887<ref>PMID:35140887</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 7s1o" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
 __TOC__
 </StructureSection>
 [[Category: Large Structures]]
-[[Category: Aramburu T]]
+[[Category: Aramburu, T]]
-[[Category: Skordalakes E]]
+[[Category: Skordalakes, E]]
+[[Category: Dna binding protein]]
+[[Category: Pot1]]
+[[Category: Telomere]]

7s1o

From Proteopedia

Revision as of 08:44, 23 February 2022

Structure of human POT1C

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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