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{{Seed}}
[[Image:2kby.jpg|left|200px]]


<!--
==The Tetramerization Domain of Human p73==
The line below this paragraph, containing "STRUCTURE_2kby", creates the "Structure Box" on the page.
<StructureSection load='2kby' size='340' side='right'caption='[[2kby]]' scene=''>
You may change the PDB parameter (which sets the PDB file loaded into the applet)
== Structural highlights ==
or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
<table><tr><td colspan='2'>[[2kby]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2KBY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2KBY FirstGlance]. <br>
or leave the SCENE parameter empty for the default display.
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2kby FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2kby OCA], [https://pdbe.org/2kby PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2kby RCSB], [https://www.ebi.ac.uk/pdbsum/2kby PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2kby ProSAT]</span></td></tr>
{{STRUCTURE_2kby|  PDB=2kby  |  SCENE=  }}
</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>
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/kb/2kby_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2kby ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
p73 and p63, the two ancestral members of the p53 family, are involved in neurogenesis, epithelial stem cell maintenance and quality control of female germ cells. The highly conserved oligomerization domain (OD) of tumor suppressor p53 is essential for its biological functions, and its structure was believed to be the prototype for all three proteins. However, we report that the ODs of p73 and p63 differ from the OD of p53 by containing an additional alpha-helix that is not present in the structure of the p53 OD. Deletion of this helix causes a dissociation of the OD into dimers; it also causes conformational instability and reduces the transcriptional activity of p73. Moreover, we show that ODs of p73 and p63 strongly interact and that a large number of different heterotetramers are supported by the additional helix. Detailed analysis shows that the heterotetramer consisting of two homodimers is thermodynamically more stable than the two homotetramers. No heterooligomerization between p53 and the p73/p63 subfamily was observed, supporting the notion of functional orthogonality within the p53 family.


===The Tetramerization Domain of Human p73===
Conformational stability and activity of p73 require a second helix in the tetramerization domain.,Coutandin D, Lohr F, Niesen FH, Ikeya T, Weber TA, Schafer B, Zielonka EM, Bullock AN, Yang A, Guntert P, Knapp S, McKeon F, Ou HD, Dotsch V Cell Death Differ. 2009 Dec;16(12):1582-9. Epub 2009 Sep 18. PMID:19763140<ref>PMID:19763140</ref>


From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2kby" style="background-color:#fffaf0;"></div>


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==See Also==
The line below this paragraph, {{ABSTRACT_PUBMED_19763140}}, adds the Publication Abstract to the page
*[[P73|P73]]
(as it appears on PubMed at http://www.pubmed.gov), where 19763140 is the PubMed ID number.
== References ==
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<references/>
{{ABSTRACT_PUBMED_19763140}}
__TOC__
 
</StructureSection>
==About this Structure==
2KBY is a 4 chains structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2KBY OCA].
 
==Reference==
<ref group="xtra">PMID:19763140</ref><references group="xtra"/>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Coutandin, D.]]
[[Category: Large Structures]]
[[Category: Doetsch, V.]]
[[Category: Coutandin D]]
[[Category: Guntert, P.]]
[[Category: Doetsch V]]
[[Category: Ikeya, T.]]
[[Category: Guntert P]]
[[Category: Loehr, F.]]
[[Category: Ikeya T]]
[[Category: Ou, H D.]]
[[Category: Loehr F]]
[[Category: Activator]]
[[Category: Ou HD]]
[[Category: Alternative splicing]]
[[Category: Anti-oncogene]]
[[Category: Apoptosis]]
[[Category: Cell cycle]]
[[Category: Dna-binding]]
[[Category: Metal-binding]]
[[Category: Nucleus]]
[[Category: Phosphoprotein]]
[[Category: Tetramerization domain]]
[[Category: Transcription]]
[[Category: Transcription regulation]]
[[Category: Ubl conjugation]]
[[Category: Zinc]]
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Sep 30 09:18:12 2009''

Latest revision as of 22:11, 29 May 2024

The Tetramerization Domain of Human p73The Tetramerization Domain of Human p73

Structural highlights

2kby is a 4 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:Solution NMR
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

p73 and p63, the two ancestral members of the p53 family, are involved in neurogenesis, epithelial stem cell maintenance and quality control of female germ cells. The highly conserved oligomerization domain (OD) of tumor suppressor p53 is essential for its biological functions, and its structure was believed to be the prototype for all three proteins. However, we report that the ODs of p73 and p63 differ from the OD of p53 by containing an additional alpha-helix that is not present in the structure of the p53 OD. Deletion of this helix causes a dissociation of the OD into dimers; it also causes conformational instability and reduces the transcriptional activity of p73. Moreover, we show that ODs of p73 and p63 strongly interact and that a large number of different heterotetramers are supported by the additional helix. Detailed analysis shows that the heterotetramer consisting of two homodimers is thermodynamically more stable than the two homotetramers. No heterooligomerization between p53 and the p73/p63 subfamily was observed, supporting the notion of functional orthogonality within the p53 family.

Conformational stability and activity of p73 require a second helix in the tetramerization domain.,Coutandin D, Lohr F, Niesen FH, Ikeya T, Weber TA, Schafer B, Zielonka EM, Bullock AN, Yang A, Guntert P, Knapp S, McKeon F, Ou HD, Dotsch V Cell Death Differ. 2009 Dec;16(12):1582-9. Epub 2009 Sep 18. PMID:19763140[4]

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

See Also

References

  1. ↑ 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
  2. ↑ Kaelin WG Jr. The emerging p53 gene family. J Natl Cancer Inst. 1999 Apr 7;91(7):594-8. PMID:10203277
  3. ↑ 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
  4. ↑ Coutandin D, Lohr F, Niesen FH, Ikeya T, Weber TA, Schafer B, Zielonka EM, Bullock AN, Yang A, Guntert P, Knapp S, McKeon F, Ou HD, Dotsch V. Conformational stability and activity of p73 require a second helix in the tetramerization domain. Cell Death Differ. 2009 Dec;16(12):1582-9. Epub 2009 Sep 18. PMID:19763140 doi:10.1038/cdd.2009.139
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