6co1

From Proteopedia

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Revision as of 06:12, 11 July 2018

Structure of human TIRR in complex with 53BP1 Tudor domains

Structural highlights

6co1 is a 6 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Gene:	NUDT16L1, SDOS, TIRR (HUMAN), TP53BP1 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[TP53B_HUMAN] Note=A chromosomal aberration involving TP53BP1 is found in a form of myeloproliferative disorder chronic with eosinophilia. Translocation t(5;15)(q33;q22) with PDGFRB creating a TP53BP1-PDGFRB fusion protein.

Function

[TIRR_HUMAN] Key regulator of TP53BP1 required to stabilize TP53BP1 and regulate its recruitment to chromatin (PubMed:28241136). In absence of DNA damage, interacts with the tandem Tudor-like domain of TP53BP1, masking the region that binds histone H4 dimethylated at 'Lys-20' (H4K20me2), thereby preventing TP53BP1 recruitment to chromatin and maintaining TP53BP1 localization to the nucleus (PubMed:28241136). Following DNA damage, ATM-induced phosphorylation of TP53BP1 and subsequent recruitment of RIF1 leads to dissociate NUDT16L1/TIRR from TP53BP1, unmasking the tandem Tudor-like domain and allowing recruitment of TP53BP1 to DNA double strand breaks (DSBs) (PubMed:28241136). Binds U8 snoRNA (PubMed:18820299).^[1] ^[2] [TP53B_HUMAN] Plays a key role in the response to DNA damage. May have a role in checkpoint signaling during mitosis. Enhances TP53-mediated transcriptional activation.^[3] ^[4]

Publication Abstract from PubMed

Dynamic protein interaction networks such as DNA double-strand break (DSB) signaling are modulated by post-translational modifications. The DNA repair factor 53BP1 is a rare example of a protein whose post-translational modification-binding function can be switched on and off. 53BP1 is recruited to DSBs by recognizing histone lysine methylation within chromatin, an activity directly inhibited by the 53BP1-binding protein TIRR. X-ray crystal structures of TIRR and a designer protein bound to 53BP1 now reveal a unique regulatory mechanism in which an intricate binding area centered on an essential TIRR arginine residue blocks the methylated-chromatin-binding surface of 53BP1. A 53BP1 separation-of-function mutation that abolishes TIRR-mediated regulation in cells renders 53BP1 hyperactive in response to DSBs, highlighting the key inhibitory function of TIRR. This 53BP1 inhibition is relieved by TIRR-interacting RNA molecules, providing proof-of-principle of RNA-triggered 53BP1 recruitment to DSBs.

Mechanism of 53BP1 activity regulation by RNA-binding TIRR and a designer protein.,Botuyan MV, Cui G, Drane P, Oliveira C, Detappe A, Brault ME, Parnandi N, Chaubey S, Thompson JR, Bragantini B, Zhao D, Chapman JR, Chowdhury D, Mer G Nat Struct Mol Biol. 2018 Jul 2. pii: 10.1038/s41594-018-0083-z. doi:, 10.1038/s41594-018-0083-z. PMID:29967538^[5]

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

References

↑ Taylor MJ, Peculis BA. Evolutionary conservation supports ancient origin for Nudt16, a nuclear-localized, RNA-binding, RNA-decapping enzyme. Nucleic Acids Res. 2008 Oct;36(18):6021-34. doi: 10.1093/nar/gkn605. Epub 2008, Sep 27. PMID:18820299 doi:http://dx.doi.org/10.1093/nar/gkn605
↑ Drane P, Brault ME, Cui G, Meghani K, Chaubey S, Detappe A, Parnandi N, He Y, Zheng XF, Botuyan MV, Kalousi A, Yewdell WT, Munch C, Harper JW, Chaudhuri J, Soutoglou E, Mer G, Chowdhury D. TIRR regulates 53BP1 by masking its histone methyl-lysine binding function. Nature. 2017 Mar 9;543(7644):211-216. doi: 10.1038/nature21358. Epub 2017 Feb 27. PMID:28241136 doi:http://dx.doi.org/10.1038/nature21358
↑ Wang B, Matsuoka S, Carpenter PB, Elledge SJ. 53BP1, a mediator of the DNA damage checkpoint. Science. 2002 Nov 15;298(5597):1435-8. Epub 2002 Oct 3. PMID:12364621 doi:10.1126/science.1076182
↑ Botuyan MV, Lee J, Ward IM, Kim JE, Thompson JR, Chen J, Mer G. Structural basis for the methylation state-specific recognition of histone H4-K20 by 53BP1 and Crb2 in DNA repair. Cell. 2006 Dec 29;127(7):1361-73. PMID:17190600 doi:10.1016/j.cell.2006.10.043
↑ Botuyan MV, Cui G, Drane P, Oliveira C, Detappe A, Brault ME, Parnandi N, Chaubey S, Thompson JR, Bragantini B, Zhao D, Chapman JR, Chowdhury D, Mer G. Mechanism of 53BP1 activity regulation by RNA-binding TIRR and a designer protein. Nat Struct Mol Biol. 2018 Jul 2. pii: 10.1038/s41594-018-0083-z. doi:, 10.1038/s41594-018-0083-z. PMID:29967538 doi:http://dx.doi.org/10.1038/s41594-018-0083-z

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6co1"

@@ Line 3: / Line 3: @@
 <StructureSection load='6co1' size='340' side='right' caption='[[6co1]], [[Resolution|resolution]] 2.18&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6co1]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6CO1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6CO1 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6co1]] is a 6 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=6CO1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6CO1 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=6co1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6co1 OCA], [http://pdbe.org/6co1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6co1 RCSB], [http://www.ebi.ac.uk/pdbsum/6co1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6co1 ProSAT]</span></td></tr>
+</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NUDT16L1, SDOS, TIRR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), TP53BP1 ([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://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6co1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6co1 OCA], [http://pdbe.org/6co1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6co1 RCSB], [http://www.ebi.ac.uk/pdbsum/6co1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6co1 ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 10: / Line 11: @@
 == Function ==
 [[http://www.uniprot.org/uniprot/TIRR_HUMAN TIRR_HUMAN]] Key regulator of TP53BP1 required to stabilize TP53BP1 and regulate its recruitment to chromatin (PubMed:28241136). In absence of DNA damage, interacts with the tandem Tudor-like domain of TP53BP1, masking the region that binds histone H4 dimethylated at 'Lys-20' (H4K20me2), thereby preventing TP53BP1 recruitment to chromatin and maintaining TP53BP1 localization to the nucleus (PubMed:28241136). Following DNA damage, ATM-induced phosphorylation of TP53BP1 and subsequent recruitment of RIF1 leads to dissociate NUDT16L1/TIRR from TP53BP1, unmasking the tandem Tudor-like domain and allowing recruitment of TP53BP1 to DNA double strand breaks (DSBs) (PubMed:28241136). Binds U8 snoRNA (PubMed:18820299).<ref>PMID:18820299</ref> <ref>PMID:28241136</ref>  [[http://www.uniprot.org/uniprot/TP53B_HUMAN TP53B_HUMAN]] Plays a key role in the response to DNA damage. May have a role in checkpoint signaling during mitosis. Enhances TP53-mediated transcriptional activation.<ref>PMID:12364621</ref> <ref>PMID:17190600</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Dynamic protein interaction networks such as DNA double-strand break (DSB) signaling are modulated by post-translational modifications. The DNA repair factor 53BP1 is a rare example of a protein whose post-translational modification-binding function can be switched on and off. 53BP1 is recruited to DSBs by recognizing histone lysine methylation within chromatin, an activity directly inhibited by the 53BP1-binding protein TIRR. X-ray crystal structures of TIRR and a designer protein bound to 53BP1 now reveal a unique regulatory mechanism in which an intricate binding area centered on an essential TIRR arginine residue blocks the methylated-chromatin-binding surface of 53BP1. A 53BP1 separation-of-function mutation that abolishes TIRR-mediated regulation in cells renders 53BP1 hyperactive in response to DSBs, highlighting the key inhibitory function of TIRR. This 53BP1 inhibition is relieved by TIRR-interacting RNA molecules, providing proof-of-principle of RNA-triggered 53BP1 recruitment to DSBs.
+Mechanism of 53BP1 activity regulation by RNA-binding TIRR and a designer protein.,Botuyan MV, Cui G, Drane P, Oliveira C, Detappe A, Brault ME, Parnandi N, Chaubey S, Thompson JR, Bragantini B, Zhao D, Chapman JR, Chowdhury D, Mer G Nat Struct Mol Biol. 2018 Jul 2. pii: 10.1038/s41594-018-0083-z. doi:, 10.1038/s41594-018-0083-z. PMID:29967538<ref>PMID:29967538</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 6co1" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Human]]
 [[Category: Botuyan, M V]]
 [[Category: Cui, G]]

6co1

From Proteopedia

Revision as of 06:12, 11 July 2018

Structure of human TIRR in complex with 53BP1 Tudor domains

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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