2i46

From Proteopedia

(Difference between revisions)

Revision as of 03:36, 25 December 2014

Crystal structure of human TPP1

Structural highlights

2i46 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Gene:	ACD, PIP1, PTOP (Homo sapiens)
Resources:	FirstGlance, OCA, RCSB, PDBsum

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]

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.

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^[6]

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

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
↑ 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

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/2i46"

@@ Line 6: / Line 6: @@
 <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=2i46 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2i46 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2i46 RCSB], [http://www.ebi.ac.uk/pdbsum/2i46 PDBsum]</span></td></tr>
 </table>
+== Function ==
+[[http://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 ==
@@ Line 19: / Line 21: @@
 </StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Baciu, P.]]
+[[Category: Baciu, P]]
-[[Category: Cech, T R.]]
+[[Category: Cech, T R]]
-[[Category: Else, T.]]
+[[Category: Else, T]]
-[[Category: Hammer, G D.]]
+[[Category: Hammer, G D]]
-[[Category: Lei, M.]]
+[[Category: Lei, M]]
-[[Category: Podell, E R.]]
+[[Category: Podell, E R]]
-[[Category: Wang, F.]]
+[[Category: Wang, F]]
-[[Category: Yang, Y T.]]
+[[Category: Yang, Y T]]
-[[Category: Zaug, A J.]]
+[[Category: Zaug, A J]]
 [[Category: Ob fold]]
 [[Category: Pot1 binding]]
 [[Category: Protein binding]]
 [[Category: Tpp1]]

2i46

From Proteopedia

Revision as of 03:36, 25 December 2014

Crystal structure of human TPP1

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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