4m7c

From Proteopedia

(Difference between revisions)

Current revision

Crystal structure of the TRF2-binding motif of SLX4 in complex with the TRFH domain of TRF2

Structural highlights

4m7c is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.05Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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.^[1] ^[2] ^[3]

Publication Abstract from PubMed

SLX4 interacts with several endonucleases to resolve structural barriers in DNA metabolism. SLX4 also interacts with telomeric protein TRF2 in human cells. The molecular mechanism of these interactions at telomeres remains unknown. Here, we report the crystal structure of the TRF2-binding motif of SLX4 (SLX4TBM) in complex with the TRFH domain of TRF2 (TRF2TRFH) and map the interactions of SLX4 with endonucleases SLX1, XPF, and MUS81. TRF2 recognizes a unique HxLxP motif on SLX4 via the peptide-binding site in its TRFH domain. Telomeric localization of SLX4 and associated nucleases depend on the SLX4-endonuclease and SLX4-TRF2 interactions and the protein levels of SLX4 and TRF2. SLX4 assembles an endonuclease toolkit that negatively regulates telomere length via SLX1-catalyzed nucleolytic resolution of telomere DNA structures. We propose that the SLX4-TRF2 complex serves as a double-layer scaffold bridging multiple endonucleases with telomeres for recombination-based telomere maintenance.

SLX4 Assembles a Telomere Maintenance Toolkit by Bridging Multiple Endonucleases with Telomeres.,Wan B, Yin J, Horvath K, Sarkar J, Chen Y, Wu J, Wan K, Lu J, Gu P, Yu EY, Lue NF, Chang S, Liu Y, Lei M Cell Rep. 2013 Sep 12;4(5):861-869. doi: 10.1016/j.celrep.2013.08.017. Epub 2013 , Sep 5. PMID:24012755^[4]

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

References

↑ van Steensel B, Smogorzewska A, de Lange T. TRF2 protects human telomeres from end-to-end fusions. Cell. 1998 Feb 6;92(3):401-13. PMID:9476899
↑ 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
↑ Ye J, Lenain C, Bauwens S, Rizzo A, Saint-Leger A, Poulet A, Benarroch D, Magdinier F, Morere J, Amiard S, Verhoeyen E, Britton S, Calsou P, Salles B, Bizard A, Nadal M, Salvati E, Sabatier L, Wu Y, Biroccio A, Londono-Vallejo A, Giraud-Panis MJ, Gilson E. TRF2 and apollo cooperate with topoisomerase 2alpha to protect human telomeres from replicative damage. Cell. 2010 Jul 23;142(2):230-42. doi: 10.1016/j.cell.2010.05.032. PMID:20655466 doi:10.1016/j.cell.2010.05.032
↑ Wan B, Yin J, Horvath K, Sarkar J, Chen Y, Wu J, Wan K, Lu J, Gu P, Yu EY, Lue NF, Chang S, Liu Y, Lei M. SLX4 Assembles a Telomere Maintenance Toolkit by Bridging Multiple Endonucleases with Telomeres. Cell Rep. 2013 Sep 12;4(5):861-869. doi: 10.1016/j.celrep.2013.08.017. Epub 2013 , Sep 5. PMID:24012755 doi:10.1016/j.celrep.2013.08.017

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/4m7c"

@@ Line 4: / Line 4: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[4m7c]] is a 4 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=4M7C OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4M7C 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=4m7c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4m7c OCA], [https://pdbe.org/4m7c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4m7c RCSB], [https://www.ebi.ac.uk/pdbsum/4m7c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4m7c ProSAT]</span></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]] 2.05&#8491;</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=4m7c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4m7c OCA], [https://pdbe.org/4m7c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4m7c RCSB], [https://www.ebi.ac.uk/pdbsum/4m7c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4m7c ProSAT]</span></td></tr>
 </table>
 == Function ==

4m7c

From Proteopedia

Current revision

Crystal structure of the TRF2-binding motif of SLX4 in complex with the TRFH domain of TRF2

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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