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| | <StructureSection load='4x34' size='340' side='right'caption='[[4x34]], [[Resolution|resolution]] 1.80Å' scene=''> | | <StructureSection load='4x34' size='340' side='right'caption='[[4x34]], [[Resolution|resolution]] 1.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4x34]] is a 4 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=4X34 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4X34 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4x34]] 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=4X34 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4X34 FirstGlance]. <br> |
| - | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ALY:N(6)-ACETYLLYSINE'>ALY</scene>, <scene name='pdbligand=MLY:N-DIMETHYL-LYSINE'>MLY</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ALY:N(6)-ACETYLLYSINE'>ALY</scene>, <scene name='pdbligand=MLY:N-DIMETHYL-LYSINE'>MLY</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">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'>[https://proteopedia.org/fgij/fg.htm?mol=4x34 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4x34 OCA], [https://pdbe.org/4x34 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4x34 RCSB], [https://www.ebi.ac.uk/pdbsum/4x34 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4x34 ProSAT]</span></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=4x34 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4x34 OCA], [http://pdbe.org/4x34 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4x34 RCSB], [http://www.ebi.ac.uk/pdbsum/4x34 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4x34 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/TP53B_HUMAN 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. | + | [https://www.uniprot.org/uniprot/TP53B_HUMAN 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 == | | == Function == |
| - | [[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> | + | [https://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;"> | | <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: Kutateladze, T G]] | + | [[Category: Kutateladze TG]] |
| - | [[Category: Tong, Q]] | + | [[Category: Tong Q]] |
| - | [[Category: Posttranslational modification]]
| + | |
| - | [[Category: Tandem tudor domain of 53bp1]]
| + | |
| - | [[Category: Transcription-transcription inhibitor complex]]
| + | |
| Structural highlights
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
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.[1] [2]
Publication Abstract from PubMed
Individual posttranslational modifications (PTMs) of p53 mediate diverse p53-dependent responses; however, much less is known about the combinatorial action of adjacent modifications. Here, we describe crosstalk between the early DNA damage response mark p53K382me2 and the surrounding PTMs that modulate binding of p53 cofactors, including 53BP1 and p300. The 1.8 A resolution crystal structure of the tandem Tudor domain (TTD) of 53BP1 in complex with p53 peptide acetylated at K381 and dimethylated at K382 (p53K381acK382me2) reveals that the dual PTM induces a conformational change in p53. The alpha-helical fold of p53K381acK382me2 positions the side chains of R379, K381ac, and K382me2 to interact with TTD concurrently, reinforcing a modular design of double PTM mimetics. Biochemical and nuclear magnetic resonance analyses show that other surrounding PTMs, including phosphorylation of serine/threonine residues of p53, affect association with TTD. Our findings suggest a novel PTM-driven conformation switch-like mechanism that may regulate p53 interactions with binding partners.
An Acetyl-Methyl Switch Drives a Conformational Change in p53.,Tong Q, Mazur SJ, Rincon-Arano H, Rothbart SB, Kuznetsov DM, Cui G, Liu WH, Gete Y, Klein BJ, Jenkins L, Mer G, Kutateladze AG, Strahl BD, Groudine M, Appella E, Kutateladze TG Structure. 2015 Feb 3;23(2):322-31. doi: 10.1016/j.str.2014.12.010. PMID:25651062[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ 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
- ↑ Tong Q, Mazur SJ, Rincon-Arano H, Rothbart SB, Kuznetsov DM, Cui G, Liu WH, Gete Y, Klein BJ, Jenkins L, Mer G, Kutateladze AG, Strahl BD, Groudine M, Appella E, Kutateladze TG. An Acetyl-Methyl Switch Drives a Conformational Change in p53. Structure. 2015 Feb 3;23(2):322-31. doi: 10.1016/j.str.2014.12.010. PMID:25651062 doi:http://dx.doi.org/10.1016/j.str.2014.12.010
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