View source for 6ijq


==Solution structure of BCL-XL bound to P73-TAD peptide==
<StructureSection load='6ijq' size='340' side='right'caption='[[6ijq]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6ijq]] is a 2 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=6IJQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6IJQ FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=6ijq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ijq OCA], [https://pdbe.org/6ijq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ijq RCSB], [https://www.ebi.ac.uk/pdbsum/6ijq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ijq ProSAT]</span></td></tr>
</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;">
== Publication Abstract from PubMed ==
In response to genotoxic stress, the tumor suppressor protein p73 induces apoptosis and cell cycle arrest. Despite extensive studies on p73-mediated apoptosis, little is known about the cytoplasmic apoptotic function of p73. Here, using H1299 lung cancer cells and diverse biochemical approaches, including colony formation, DNA fragmentation, GST pull-down, and apoptosis assays along with NMR spectroscopy, we show that p73 induces transcription-independent apoptosis via its transactivation domain (TAD) through a mitochondrial pathway and that this apoptosis is mediated by the interaction between p73-TAD and the anti-apoptotic protein B-cell lymphoma-extra large (Bcl-XL or BCL2L1). This binding disrupted an interaction between Bcl-XL and the pro-apoptotic protein BH3-interacting domain death agonist (BID). In particular, we found that a 16-mer p73-TAD peptide motif (p73-TAD16) mediates transcription-independent apoptosis, accompanied by cytochrome c release from the mitochondria, by interacting with Bcl-XL Interestingly, the structure of the Bcl-XL-p73-TAD16 peptide complex revealed a novel mechanism of Bcl-XL recognition by p73-TAD. We observed that the alpha-helical p73-TAD16 peptide binds to a non-canonical site in Bcl-XL, comprising the BH1, BH2, and BH3 domains in an orientation opposite to those of pro-apoptotic BH3 peptides. Taken together, our results indicate that the cytoplasmic apoptotic function of p73 is mediated through a non-canonical mode of Bcl-XL recognition. This finding sheds light on a critical transcription-independent, p73-mediated mechanism for apoptosis induction, which has potential implications for anticancer therapy.

Cytoplasmic pro-apoptotic function of the tumor suppressor p73 is mediated through a modified mode of recognition of the anti-apoptotic regulator Bcl-XL.,Yoon MK, Kim BY, Lee JY, Ha JH, Kim SA, Lee DH, Lee MS, Lee MK, Choi JS, Cho JH, Kim JH, Kim S, Song J, Park SG, Park BC, Bae KH, Choi SU, Chi SW J Biol Chem. 2018 Nov 14. pii: RA118.003061. doi: 10.1074/jbc.RA118.003061. PMID:30429221<ref>PMID:30429221</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6ijq" style="background-color:#fffaf0;"></div>

==See Also==
*[[B-cell lymphoma proteins 3D structures|B-cell lymphoma proteins 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Chi S-W]]
[[Category: Ha J-H]]
[[Category: Lee M-S]]
[[Category: Yoon M-K]]