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| | ==structure of p73 DNA binding domain tetramer modulates p73 transactivation== | | ==structure of p73 DNA binding domain tetramer modulates p73 transactivation== |
| - | <StructureSection load='3vd2' size='340' side='right' caption='[[3vd2]], [[Resolution|resolution]] 4.00Å' scene=''> | + | <StructureSection load='3vd2' size='340' side='right'caption='[[3vd2]], [[Resolution|resolution]] 4.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3vd2]] is a 12 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3VD2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3VD2 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3vd2]] is a 12 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=3VD2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3VD2 FirstGlance]. <br> |
| - | </td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene><br> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 4Å</td></tr> |
| - | <tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3vd1|3vd1]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3vd2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vd2 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3vd2 RCSB], [http://www.ebi.ac.uk/pdbsum/3vd2 PDBsum]</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=3vd2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vd2 OCA], [https://pdbe.org/3vd2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3vd2 RCSB], [https://www.ebi.ac.uk/pdbsum/3vd2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3vd2 ProSAT]</span></td></tr> |
| - | <table> | + | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/P73_HUMAN P73_HUMAN] Participates in the apoptotic response to DNA damage. Isoforms containing the transactivation domain are pro-apoptotic, isoforms lacking the domain are anti-apoptotic and block the function of p53 and transactivating p73 isoforms. May be a tumor suppressor protein.<ref>PMID:11753569</ref> <ref>PMID:10203277</ref> <ref>PMID:18174154</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 3vd2" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[P73|P73]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| - | [[Category: Ethayathulla, A S.]] | + | [[Category: Large Structures]] |
| - | [[Category: Nguyen, S.]] | + | [[Category: Ethayathulla AS]] |
| - | [[Category: Tse, P W.]] | + | [[Category: Nguyen S]] |
| - | [[Category: Viadiu, H.]] | + | [[Category: Tse PW]] |
| - | [[Category: Antitumor protein-dna complex]] | + | [[Category: Viadiu H]] |
| - | [[Category: Beta-immunoglobulin-like fold]]
| + | |
| - | [[Category: Dna]]
| + | |
| - | [[Category: Protein dna complex]]
| + | |
| - | [[Category: Tumour suppressor]]
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| Structural highlights
Function
P73_HUMAN Participates in the apoptotic response to DNA damage. Isoforms containing the transactivation domain are pro-apoptotic, isoforms lacking the domain are anti-apoptotic and block the function of p53 and transactivating p73 isoforms. May be a tumor suppressor protein.[1] [2] [3]
Publication Abstract from PubMed
The transcription factor p73 triggers developmental pathways and overlaps stress-induced p53 transcriptional pathways. How p53-family response elements determine and regulate transcriptional specificity remains an unsolved problem. In this work, we have determined the first crystal structures of p73 DNA-binding domain tetramer bound to response elements with spacers of different length. The structure and function of the adaptable tetramer are determined by the distance between two half-sites. The structures with zero and one base-pair spacers show compact p73 DNA-binding domain tetramers with large tetramerization interfaces; a two base-pair spacer results in DNA unwinding and a smaller tetramerization interface, whereas a four base-pair spacer hinders tetramerization. Functionally, p73 is more sensitive to spacer length than p53, with one base-pair spacer reducing 90% of transactivation activity and longer spacers reducing transactivation to basal levels. Our results establish the quaternary structure of the p73 DNA-binding domain required as a scaffold to promote transactivation.
Structure of p73 DNA-binding domain tetramer modulates p73 transactivation.,Ethayathulla AS, Tse PW, Monti P, Nguyen S, Inga A, Fronza G, Viadiu H Proc Natl Acad Sci U S A. 2012 Apr 2. PMID:22474346[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Grob TJ, Novak U, Maisse C, Barcaroli D, Luthi AU, Pirnia F, Hugli B, Graber HU, De Laurenzi V, Fey MF, Melino G, Tobler A. Human delta Np73 regulates a dominant negative feedback loop for TAp73 and p53. Cell Death Differ. 2001 Dec;8(12):1213-23. PMID:11753569 doi:10.1038/sj.cdd.4400962
- ↑ Kaelin WG Jr. The emerging p53 gene family. J Natl Cancer Inst. 1999 Apr 7;91(7):594-8. PMID:10203277
- ↑ Koida N, Ozaki T, Yamamoto H, Ono S, Koda T, Ando K, Okoshi R, Kamijo T, Omura K, Nakagawara A. Inhibitory role of Plk1 in the regulation of p73-dependent apoptosis through physical interaction and phosphorylation. J Biol Chem. 2008 Mar 28;283(13):8555-63. doi: 10.1074/jbc.M710608200. Epub 2008 , Jan 3. PMID:18174154 doi:10.1074/jbc.M710608200
- ↑ Ethayathulla AS, Tse PW, Monti P, Nguyen S, Inga A, Fronza G, Viadiu H. Structure of p73 DNA-binding domain tetramer modulates p73 transactivation. Proc Natl Acad Sci U S A. 2012 Apr 2. PMID:22474346 doi:10.1073/pnas.1115463109
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