View source for 2mej


==Solution Structure of the Complex Between BCL-xL and the p53 Core Domain determined with PRE restraints==
<StructureSection load='2mej' size='340' side='right'caption='[[2mej]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2mej]] 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=2MEJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2MEJ 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='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 id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2mej FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2mej OCA], [https://pdbe.org/2mej PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2mej RCSB], [https://www.ebi.ac.uk/pdbsum/2mej PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2mej ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/B2CL1_HUMAN B2CL1_HUMAN] Potent inhibitor of cell death. Inhibits activation of caspases (By similarity). Appears to regulate cell death by blocking the voltage-dependent anion channel (VDAC) by binding to it and preventing the release of the caspase activator, CYC1, from the mitochondrial membrane. Also acts as a regulator of G2 checkpoint and progression to cytokinesis during mitosis.<ref>PMID:19917720</ref> <ref>PMID:21840391</ref>   Isoform Bcl-X(S) promotes apoptosis.<ref>PMID:19917720</ref> <ref>PMID:21840391</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Under conditions of genotoxic stress, human p53 activates the apoptotic effectors BAX or BAK to result in mitochondrial outer-membrane permeabilization and apoptosis. Antiapoptotic BCL-2 family member BCL-xL opposes this activity by sequestering cytosolic p53 via association with its DNA-binding domain, an interaction enhanced by p53 tetramerization. Here we characterized the BCL-xL-p53 complex by NMR spectroscopy and modulated it through mutagenesis to determine the relative contributions of BCL-xL's interactions with p53 or other BCL-2 family proteins to the BCL-xL-dependent inhibition of UV irradiation-induced apoptosis. Under our experimental conditions, one-third of the antiapoptotic activity of BCL-xL was mediated by p53 sequestration and the remaining two-thirds through sequestration of proapoptotic BCL-2 family members. Our studies define the contributions of cytosolic p53 to UV irradiation-induced apoptosis and provide opportunities to explore its contributions to other p53-dependent apoptotic signaling pathways.

The DNA-binding domain mediates both nuclear and cytosolic functions of p53.,Follis AV, Llambi F, Ou L, Baran K, Green DR, Kriwacki RW Nat Struct Mol Biol. 2014 Jun;21(6):535-43. doi: 10.1038/nsmb.2829. Epub 2014 May, 11. PMID:24814347<ref>PMID:24814347</ref>

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

==See Also==
*[[B-cell lymphoma proteins 3D structures|B-cell lymphoma proteins 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Grace CR]]
[[Category: Kriwacki RW]]
[[Category: Viacava Follis A]]