2me8: Difference between revisions
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==Solution Structure of BCL-xL in its p53-bound conformation determined with selective isotope labelling of I,L,V sidechains== | ==Solution Structure of BCL-xL in its p53-bound conformation determined with selective isotope labelling of I,L,V sidechains== | ||
<StructureSection load='2me8' size='340' side='right' caption='[[2me8 | <StructureSection load='2me8' size='340' side='right'caption='[[2me8]]' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2me8]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ME8 OCA]. < | <table><tr><td colspan='2'>[[2me8]] is a 1 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=2ME8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2ME8 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><td class="sblockLbl"><b> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2me8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2me8 OCA], [https://pdbe.org/2me8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2me8 RCSB], [https://www.ebi.ac.uk/pdbsum/2me8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2me8 ProSAT]</span></td></tr> | ||
<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | </table> | ||
<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®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2me8" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[B-cell lymphoma proteins 3D structures|B-cell lymphoma proteins 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Grace CR]] | ||
[[Category: | [[Category: Kriwacki RW]] | ||
[[Category: | [[Category: Viacava Follis A]] | ||
Latest revision as of 06:04, 15 May 2024
Solution Structure of BCL-xL in its p53-bound conformation determined with selective isotope labelling of I,L,V sidechains
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