5wqd - Revision history

OCA at 16:51, 8 November 2023

OCA — Wed, 08 Nov 2023 16:51:12 GMT

←Older revision		Revision as of 16:51, 8 November 2023
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	<StructureSection load='5wqd' size='340' side='right'caption='[[5wqd]], [[Resolution\|resolution]] 3.00Å' scene=''>		<StructureSection load='5wqd' size='340' side='right'caption='[[5wqd]], [[Resolution\|resolution]] 3.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5wqd]] is a 14 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WQD OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=5WQD FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5wqd]] is a 14 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=5WQD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5WQD FirstGlance]. <br>
-	</td></tr><tr id='~~gene~~'><td class="sblockLbl"><b>[[~~Gene~~\|~~Gene~~:]]</b></td><td class="sblockDat">~~TERF2~~, ~~TRBF2, TRF2 (~~[~~http://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]] 3Å</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=5wqd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wqd OCA], [~~http~~://pdbe.org/5wqd PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5wqd RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5wqd PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5wqd 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=5wqd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wqd OCA], [https://pdbe.org/5wqd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5wqd RCSB], [https://www.ebi.ac.uk/pdbsum/5wqd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5wqd ProSAT]</span></td></tr>
	</table>		</table>
-	== Disease ==
-	[[http://www.uniprot.org/uniprot/NBN_HUMAN NBN_HUMAN]] Nijmegen breakage syndrome;Hereditary breast and ovarian cancer syndrome;Familial prostate cancer. The disease is caused by mutations affecting the gene represented in this entry. Disease susceptibility is associated with variations affecting the gene represented in this entry. Disease susceptibility may be associated with variations affecting the gene represented in this entry. Defects in NBN might play a role in the pathogenesis of childhood acute lymphoblastic leukemia (ALL).<ref>PMID:11325820</ref>
	== Function ==		== Function ==
-	[~~[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> [[http://www.uniprot.org/uniprot/NBN_HUMAN NBN_HUMAN]] Component of the MRE11-RAD50-NBN (MRN complex) which plays a critical role in the cellular response to DNA damage and the maintenance of chromosome integrity. The complex is involved in double-strand break (DSB) repair, DNA recombination, maintenance of telomere integrity, cell cycle checkpoint control and meiosis. The complex possesses single-strand endonuclease activity and double-strand-specific 3'-5' exonuclease activity, which are provided by MRE11. RAD50 may be required to bind DNA ends and hold them in close proximity. NBN modulate the DNA damage signal sensing by recruiting PI3/PI4-kinase family members ATM, ATR, and probably DNA-PKcs to the DNA damage sites and activating their functions. It can also recruit MRE11 and RAD50 to the proximity of DSBs by an interaction with the histone H2AX. NBN also functions in telomere length maintenance by generating the 3' overhang which serves as a primer for telomerase dependent telomere elongation. NBN is a major player in the control of intra-S-phase checkpoint and there is some evidence that NBN is involved in G1 and G2 checkpoints. The roles of NBS1/MRN encompass DNA damage sensor, signal transducer, and effector, which enable cells to maintain DNA integrity and genomic stability. Forms a complex with RBBP8 to link DNA double-strand break sensing to resection. Enhances AKT1 phosphorylation possibly by association with the mTORC2 complex.<ref>PMID:10888888</ref> <ref>PMID:15616588</ref> <ref>PMID:19759395</ref> <ref>PMID:23762398</ref> <ref>PMID:9705271</ref>	+	[https://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;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Chen, Y]]	+	[[Category: Chen Y]]
-	[[Category: Hu, C]]	+	[[Category: Hu C]]
-	[[Category: Lei, M]]	+	[[Category: Lei M]]
-	~~[[Category: Cell cycle]]~~	+
-	~~[[Category: Dna damage response]]~~	+
-	~~[[Category: Shelterin complex]]~~	+
-	~~[[Category: Telomere~~]]	+

OCA at 07:14, 7 October 2020

OCA — Wed, 07 Oct 2020 07:14:22 GMT

←Older revision		Revision as of 07:14, 7 October 2020
Line 1:		Line 1:

	==Crystal structure of TRF2 TRFH in complex with an NBS1 peptide==		==Crystal structure of TRF2 TRFH in complex with an NBS1 peptide==
-	<StructureSection load='5wqd' size='340' side='right' caption='[[5wqd]], [[Resolution\|resolution]] 3.00Å' scene=''>	+	<StructureSection load='5wqd' size='340' side='right'caption='[[5wqd]], [[Resolution\|resolution]] 3.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5wqd]] is a 14 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WQD OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5WQD FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5wqd]] is a 14 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WQD OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5WQD FirstGlance]. <br>
-	</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=5wqd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wqd OCA], [http://pdbe.org/5wqd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5wqd RCSB], [http://www.ebi.ac.uk/pdbsum/5wqd PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5wqd ProSAT]</span></td></tr>	+	</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">TERF2, TRBF2, TRF2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=5wqd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wqd OCA], [http://pdbe.org/5wqd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5wqd RCSB], [http://www.ebi.ac.uk/pdbsum/5wqd PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5wqd ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 23:		Line 24:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Chen, Y]]		[[Category: Chen, Y]]
	[[Category: Hu, C]]		[[Category: Hu, C]]

OCA at 16:44, 9 March 2017

OCA — Thu, 09 Mar 2017 16:44:45 GMT

←Older revision		Revision as of 16:44, 9 March 2017
Line 1:		Line 1:
-	'''Unreleased structure'''

-	The entry ~~5wqd~~ is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==Crystal structure of TRF2 TRFH in complex with an NBS1 peptide==
		+	<StructureSection load='5wqd' size='340' side='right' caption='[[5wqd]], [[Resolution\|resolution]] 3.00Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5wqd]] is a 14 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WQD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5WQD FirstGlance]. <br>
		+	</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=5wqd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wqd OCA], [http://pdbe.org/5wqd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5wqd RCSB], [http://www.ebi.ac.uk/pdbsum/5wqd PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5wqd ProSAT]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/NBN_HUMAN NBN_HUMAN]] Nijmegen breakage syndrome;Hereditary breast and ovarian cancer syndrome;Familial prostate cancer. The disease is caused by mutations affecting the gene represented in this entry. Disease susceptibility is associated with variations affecting the gene represented in this entry. Disease susceptibility may be associated with variations affecting the gene represented in this entry. Defects in NBN might play a role in the pathogenesis of childhood acute lymphoblastic leukemia (ALL).<ref>PMID:11325820</ref>
		+	== Function ==
		+	[[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> [[http://www.uniprot.org/uniprot/NBN_HUMAN NBN_HUMAN]] Component of the MRE11-RAD50-NBN (MRN complex) which plays a critical role in the cellular response to DNA damage and the maintenance of chromosome integrity. The complex is involved in double-strand break (DSB) repair, DNA recombination, maintenance of telomere integrity, cell cycle checkpoint control and meiosis. The complex possesses single-strand endonuclease activity and double-strand-specific 3'-5' exonuclease activity, which are provided by MRE11. RAD50 may be required to bind DNA ends and hold them in close proximity. NBN modulate the DNA damage signal sensing by recruiting PI3/PI4-kinase family members ATM, ATR, and probably DNA-PKcs to the DNA damage sites and activating their functions. It can also recruit MRE11 and RAD50 to the proximity of DSBs by an interaction with the histone H2AX. NBN also functions in telomere length maintenance by generating the 3' overhang which serves as a primer for telomerase dependent telomere elongation. NBN is a major player in the control of intra-S-phase checkpoint and there is some evidence that NBN is involved in G1 and G2 checkpoints. The roles of NBS1/MRN encompass DNA damage sensor, signal transducer, and effector, which enable cells to maintain DNA integrity and genomic stability. Forms a complex with RBBP8 to link DNA double-strand break sensing to resection. Enhances AKT1 phosphorylation possibly by association with the mTORC2 complex.<ref>PMID:10888888</ref> <ref>PMID:15616588</ref> <ref>PMID:19759395</ref> <ref>PMID:23762398</ref> <ref>PMID:9705271</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Telomeres employ TRF2 to protect chromosome ends from activating the DNA damage sensor MRE11-RAD50-NBS1 (MRN), thereby repressing ATM-dependent DNA damage checkpoint responses. How TRF2 prevents MRN activation at dysfunctional telomeres is unclear. Here, we show that the phosphorylation status of NBS1 determines the repair pathway choice of dysfunctional telomeres. The crystal structure of the TRF2-NBS1 complex at 3.0 A resolution shows that the NBS1 429YQLSP433 motif interacts specifically with the TRF2TRFH domain. Phosphorylation of NBS1 serine 432 by CDK2 in S/G2 dissociates NBS1 from TRF2, promoting TRF2-Apollo/SNM1B complex formation and the protection of leading-strand telomeres. Classical-NHEJ-mediated repair of telomeres lacking TRF2 requires phosphorylated NBS1S432 to activate ATM, while interaction of de-phosphorylated NBS1S432 with TRF2 promotes alternative-NHEJ repair of telomeres lacking POT1-TPP1. Our work advances understanding of how the TRF2TRFH domain orchestrates telomere end protection and reveals how the phosphorylation status of the NBS1S432 dictates repair pathway choice of dysfunctional telomeres.

-	~~Authors:~~ Hu, C., Chen, Y., Lei, M.	+	NBS1 Phosphorylation Status Dictates Repair Choice of Dysfunctional Telomeres.,Rai R, Hu C, Broton C, Chen Y, Lei M, Chang S Mol Cell. 2017 Mar 2;65(5):801-817.e4. doi: 10.1016/j.molcel.2017.01.016. Epub, 2017 Feb 16. PMID:28216226<ref>PMID:28216226</ref>

-	~~Description: Crystal structure~~ of ~~TRF2 TRFH in complex with an NBS1 peptide~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[Category: Unreleased Structures]]~~	+	</div>
-	~~[[Category~~: ~~Lei, M]]~~	+	<div class="pdbe-citations 5wqd" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
	[[Category: Chen, Y]]		[[Category: Chen, Y]]
	[[Category: Hu, C]]		[[Category: Hu, C]]
		+	[[Category: Lei, M]]
		+	[[Category: Cell cycle]]
		+	[[Category: Dna damage response]]
		+	[[Category: Shelterin complex]]
		+	[[Category: Telomere]]

OCA at 15:21, 2 January 2017

OCA — Mon, 02 Jan 2017 15:21:55 GMT

←Older revision		Revision as of 15:21, 2 January 2017
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 5wqd is ON HOLD	+	The entry 5wqd is ON HOLD until Paper Publication

	Authors: Hu, C., Chen, Y., Lei, M.		Authors: Hu, C., Chen, Y., Lei, M.

-	Description: Crystal structure of TRF2 TRFH in complex with a NBS1 peptide	+	Description: Crystal structure of TRF2 TRFH in complex with an NBS1 peptide
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
	[[Category: Lei, M]]		[[Category: Lei, M]]
	[[Category: Chen, Y]]		[[Category: Chen, Y]]
	[[Category: Hu, C]]		[[Category: Hu, C]]

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

OCA — Fri, 09 Dec 2016 18:17:08 GMT

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

←Older revision

Revision as of 18:17, 9 December 2016

OCA: New page: '''Unreleased structure''' The entry 5wqd is ON HOLD Authors: Hu, C., Chen, Y., Lei, M. Description: Crystal structure of TRF2 TRFH in complex with a NBS1 peptide [[Category: Unrelease...

OCA — Fri, 09 Dec 2016 18:17:06 GMT

New page: '''Unreleased structure''' The entry 5wqd is ON HOLD Authors: Hu, C., Chen, Y., Lei, M. Description: Crystal structure of TRF2 TRFH in complex with a NBS1 peptide [[Category: Unrelease...

New page

'''Unreleased structure'''

The entry 5wqd is ON HOLD

Authors: Hu, C., Chen, Y., Lei, M.

Description: Crystal structure of TRF2 TRFH in complex with a NBS1 peptide
[[Category: Unreleased Structures]]
[[Category: Lei, M]]
[[Category: Chen, Y]]
[[Category: Hu, C]]