5hoc: Difference between revisions
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==p73 homo-tetramerization domain mutant II== | ==p73 homo-tetramerization domain mutant II== | ||
<StructureSection load='5hoc' size='340' side='right' caption='[[5hoc]], [[Resolution|resolution]] 1.36Å' scene=''> | <StructureSection load='5hoc' size='340' side='right'caption='[[5hoc]], [[Resolution|resolution]] 1.36Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5hoc]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5HOC OCA]. For a <b>guided tour on the structure components</b> use [http:// | <table><tr><td colspan='2'>[[5hoc]] is a 2 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=5HOC OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5HOC FirstGlance]. <br> | ||
</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2kby|2kby]], [[4a9z|4a9z]], [[2nb1|2nb1]], [[5hob|5hob]]</td></tr> | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2kby|2kby]], [[4a9z|4a9z]], [[2nb1|2nb1]], [[5hob|5hob]]</td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http:// | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TP73, P73 ([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://proteopedia.org/fgij/fg.htm?mol=5hoc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5hoc OCA], [http://pdbe.org/5hoc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5hoc RCSB], [http://www.ebi.ac.uk/pdbsum/5hoc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5hoc ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | == Function == | ||
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</div> | </div> | ||
<div class="pdbe-citations 5hoc" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 5hoc" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[P73|P73]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Human]] | |||
[[Category: Large Structures]] | |||
[[Category: Coutandin, D]] | [[Category: Coutandin, D]] | ||
[[Category: Dotsch, V]] | [[Category: Dotsch, V]] | ||
Revision as of 11:25, 27 May 2020
p73 homo-tetramerization domain mutant IIp73 homo-tetramerization domain mutant II
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 PubMedMembers of the p53 tumor-suppressor family are expressed as multiple isoforms. Isoforms with an N-terminal transactivation domain are transcriptionally active, while those ones lacking this domain often inhibit the transcriptional activity of other family members. In squamous cell carcinomas, the high expression level of DeltaNp63alpha inhibits the tumor-suppressor function of TAp73beta. This can in principle be due to blocking of the promoter or by direct interaction between both proteins. p63 and p73 can hetero-oligomerize through their tetramerization domains and a hetero-tetramer consisting of two p63 and two p73 molecules is thermodynamically more stable than both homo-tetramers. Here we show that cells expressing both p63 and p73 exist in mouse epidermis and hair follicle and that hetero-tetramer complexes can be detected by immunoprecipitation in differentiating keratinocytes. Through structure determination of the hetero-tetramer, we reveal why this hetero-tetramer is the thermodynamically preferred species. We have created mutants that exclusively form either hetero-tetramers or homo-tetramers, allowing to investigate the function of these p63/p73 hetero-tetramers. Using these tools, we show that inhibition of TAp73beta in squamous cell carcinomas is due to promoter squelching and not direct interaction.Cell Death and Differentiation advance online publication, 7 October 2016; doi:10.1038/cdd.2016.83. Mechanism of TAp73 inhibition by DeltaNp63 and structural basis of p63/p73 hetero-tetramerization.,Gebel J, Luh LM, Coutandin D, Osterburg C, Lohr F, Schafer B, Frombach AS, Sumyk M, Buchner L, Krojer T, Salah E, Mathea S, Guntert P, Knapp S, Dotsch V Cell Death Differ. 2016 Oct 7. doi: 10.1038/cdd.2016.83. PMID:27716744[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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