OCA at 07:01, 14 October 2020

OCA — Wed, 14 Oct 2020 07:01:20 GMT

←Older revision		Revision as of 07:01, 14 October 2020
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	==Crystal structure of the human TIN2-TPP1-TRF2 telomeric complex==		==Crystal structure of the human TIN2-TPP1-TRF2 telomeric complex==
-	<StructureSection load='5xyf' size='340' side='right' caption='[[5xyf]], [[Resolution\|resolution]] 2.20Å' scene=''>	+	<StructureSection load='5xyf' size='340' side='right'caption='[[5xyf]], [[Resolution\|resolution]] 2.20Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5xyf]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5XYF OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5XYF FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5xyf]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5XYF OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5XYF FirstGlance]. <br>
	</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr>		</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></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=5xyf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xyf OCA], [http://pdbe.org/5xyf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5xyf RCSB], [http://www.ebi.ac.uk/pdbsum/5xyf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5xyf ProSAT]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5xyf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xyf OCA], [http://pdbe.org/5xyf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5xyf RCSB], [http://www.ebi.ac.uk/pdbsum/5xyf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5xyf ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 24:		Line 24:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Large Structures]]
	[[Category: Chen, Y]]		[[Category: Chen, Y]]
	[[Category: Hu, C]]		[[Category: Hu, C]]

OCA at 07:01, 13 December 2017

OCA — Wed, 13 Dec 2017 07:01:38 GMT

←Older revision		Revision as of 07:01, 13 December 2017
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5xyf is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==Crystal structure of the human TIN2-TPP1-TRF2 telomeric complex==
		+	<StructureSection load='5xyf' size='340' side='right' caption='[[5xyf]], [[Resolution\|resolution]] 2.20Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5xyf]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5XYF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5XYF FirstGlance]. <br>
		+	</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></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=5xyf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xyf OCA], [http://pdbe.org/5xyf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5xyf RCSB], [http://www.ebi.ac.uk/pdbsum/5xyf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5xyf ProSAT]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/TINF2_HUMAN TINF2_HUMAN]] Defects in TINF2 are a cause of dyskeratosis congenita autosomal dominant type 3 (DKCA3) [MIM:[http://omim.org/entry/613990 613990]]. A rare multisystem disorder caused by defective telomere maintenance. It is characterized by progressive bone marrow failure, and the clinical triad of reticulated skin hyperpigmentation, nail dystrophy, and mucosal leukoplakia. Common but variable features include premature graying, aplastic anemia, low platelets, osteoporosis, pulmonary fibrosis, and liver fibrosis among others. Early mortality is often associated with bone marrow failure, infections, fatal pulmonary complications, or malignancy.<ref>PMID:18252230</ref> Defects in TINF2 are a cause of retinopathy exudative with bone marrow failure (ERBMF) [MIM:[http://omim.org/entry/268130 268130]]; also known as Revesz syndrome. ERBMF is characterized by bilateral exudative retinopathy, bone marrow hypoplasia, nail dystrophy, fine hair, cerebellar hypoplasia, and growth retardation.<ref>PMID:18252230</ref>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/TINF2_HUMAN TINF2_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. Plays a role in shelterin complex assembly. Isoform 1 may have additional role in tethering telomeres to the nuclear matrix.<ref>PMID:16166375</ref> <ref>PMID:16880378</ref> <ref>PMID:19229133</ref> [[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> [[http://www.uniprot.org/uniprot/TERF2_HUMAN TERF2_HUMAN]] Binds the telomeric double-stranded 5'-TTAGGG-3' repeat and plays a central role in telomere maintenance and protection against end-to-end fusion of chromosomes. In addition to its telomeric DNA-binding role, required to recruit a number of factors and enzymes required for telomere protection, including the shelterin complex, TERF2IP/RAP1 and DCLRE1B/Apollo. Component of the shelterin complex (telosome) that is involved in the regulation of telomere length and protection. Shelterin associates with arrays of double-stranded 5'-TTAGGG-3' 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. Together with DCLRE1B/Apollo, plays a key role in telomeric loop (T loop) formation by generating 3' single-stranded overhang at the leading end telomeres: T loops have been proposed to protect chromosome ends from degradation and repair. Required both to recruit DCLRE1B/Apollo to telomeres and activate the exonuclease activity of DCLRE1B/Apollo. Preferentially binds to positive supercoiled DNA. Together with DCLRE1B/Apollo, required to control the amount of DNA topoisomerase (TOP1, TOP2A and TOP2B) needed for telomere replication during fork passage and prevent aberrant telomere topology. Recruits TERF2IP/RAP1 to telomeres, thereby participating in to repressing homology-directed repair (HDR), which can affect telomere length.<ref>PMID:9476899</ref> <ref>PMID:16166375</ref> <ref>PMID:20655466</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Telomeres are nucleoprotein complexes that play essential roles in protecting chromosome ends. Mammalian telomeres consist of repetitive DNA sequences bound by the shelterin complex. In this complex, the POT1-TPP1 heterodimer binds to single-stranded telomeric DNAs, while TRF1 and TRF2-RAP1 interact with double-stranded telomeric DNAs. TIN2, the linchpin of this complex, simultaneously interacts with TRF1, TRF2, and TPP1 to mediate the stable assembly of the shelterin complex. However, the molecular mechanism by which TIN2 interacts with these proteins to orchestrate telomere protection remains poorly understood. Here, we report the crystal structure of the N-terminal domain of TIN2 in complex with TIN2-binding motifs from TPP1 and TRF2, revealing how TIN2 interacts cooperatively with TPP1 and TRF2. Unexpectedly, TIN2 contains a telomeric repeat factor homology (TRFH)-like domain that functions as a protein-protein interaction platform. Structure-based mutagenesis analyses suggest that TIN2 plays an important role in maintaining the stable shelterin complex required for proper telomere end protection.

-	~~Authors:~~ Hu, C., ~~Chen~~, Y.	+	Structural and functional analyses of the mammalian TIN2-TPP1-TRF2 telomeric complex.,Hu C, Rai R, Huang C, Broton C, Long J, Xu Y, Xue J, Lei M, Chang S, Chen Y Cell Res. 2017 Dec;27(12):1485-1502. doi: 10.1038/cr.2017.144. Epub 2017 Nov 21. PMID:29160297<ref>PMID:29160297</ref>

-	~~Description: Crystal structure~~ of the ~~human TIN2~~-~~TPP1~~-~~TRF2 telomeric complex~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[Category~~: ~~Unreleased Structures]]~~	+	</div>
		+	<div class="pdbe-citations 5xyf" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
	[[Category: Chen, Y]]		[[Category: Chen, Y]]
	[[Category: Hu, C]]		[[Category: Hu, C]]
		+	[[Category: Protein binding]]
		+	[[Category: Shelterin complex]]
		+	[[Category: Telomere]]

OCA: Protected "5xyf" [edit=sysop:move=sysop]

OCA — Wed, 27 Sep 2017 15:54:59 GMT

Protected "5xyf" [edit=sysop:move=sysop]

←Older revision

Revision as of 15:54, 27 September 2017

OCA: New page: '''Unreleased structure''' The entry 5xyf is ON HOLD until Paper Publication Authors: Hu, C., Chen, Y. Description: Crystal structure of the human TIN2-TPP1-TRF2 telomeric complex [[Ca...

OCA — Wed, 27 Sep 2017 15:54:58 GMT

New page: '''Unreleased structure''' The entry 5xyf is ON HOLD until Paper Publication Authors: Hu, C., Chen, Y. Description: Crystal structure of the human TIN2-TPP1-TRF2 telomeric complex [[Ca...

New page

'''Unreleased structure'''

The entry 5xyf is ON HOLD until Paper Publication

Authors: Hu, C., Chen, Y.

Description: Crystal structure of the human TIN2-TPP1-TRF2 telomeric complex
[[Category: Unreleased Structures]]
[[Category: Chen, Y]]
[[Category: Hu, C]]

5xyf - Revision history

OCA at 07:01, 14 October 2020

OCA at 07:01, 13 December 2017

OCA: Protected "5xyf" [edit=sysop:move=sysop]

OCA: New page: '''Unreleased structure''' The entry 5xyf is ON HOLD until Paper Publication Authors: Hu, C., Chen, Y. Description: Crystal structure of the human TIN2-TPP1-TRF2 telomeric complex [[Ca...