4hnj

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[[Image:4hnj.png|left|200px]]
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==Crystallographic structure of BCL-xL domain-swapped dimer in complex with PUMA BH3 peptide at 2.9A resolution==
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<StructureSection load='4hnj' size='340' side='right' caption='[[4hnj]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[4hnj]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4HNJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4HNJ FirstGlance]. <br>
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</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2m04|2m04]], [[2m03|2m03]]</td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BCL2L1, BCL2L, BCLX ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4hnj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hnj OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4hnj RCSB], [http://www.ebi.ac.uk/pdbsum/4hnj PDBsum]</span></td></tr>
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</table>
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== Function ==
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[[http://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>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Following DNA damage, nuclear p53 induces the expression of PUMA, a BH3-only protein that binds and inhibits the antiapoptotic BCL-2 repertoire, including BCL-xL. PUMA, unique among BH3-only proteins, disrupts the interaction between cytosolic p53 and BCL-xL, allowing p53 to promote apoptosis via direct activation of the BCL-2 effector molecules BAX and BAK. Structural investigations using NMR spectroscopy and X-ray crystallography revealed that PUMA binding induced partial unfolding of two alpha-helices within BCL-xL. Wild-type PUMA or a PUMA mutant incapable of causing binding-induced unfolding of BCL-xL equivalently inhibited the antiapoptotic BCL-2 repertoire to sensitize for death receptor-activated apoptosis, but only wild-type PUMA promoted p53-dependent, DNA damage-induced apoptosis. Our data suggest that PUMA-induced partial unfolding of BCL-xL disrupts interactions between cytosolic p53 and BCL-xL, releasing the bound p53 to initiate apoptosis. We propose that regulated unfolding of BCL-xL provides a mechanism to promote PUMA-dependent signaling within the apoptotic pathways.
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{{STRUCTURE_4hnj| PDB=4hnj | SCENE= }}
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PUMA binding induces partial unfolding within BCL-xL to disrupt p53 binding and promote apoptosis.,Follis AV, Chipuk JE, Fisher JC, Yun MK, Grace CR, Nourse A, Baran K, Ou L, Min L, White SW, Green DR, Kriwacki RW Nat Chem Biol. 2013 Jan 20. doi: 10.1038/nchembio.1166. PMID:23340338<ref>PMID:23340338</ref>
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===Crystallographic structure of BCL-xL domain-swapped dimer in complex with PUMA BH3 peptide at 2.9A resolution===
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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{{ABSTRACT_PUBMED_23340338}}
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== References ==
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<references/>
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==About this Structure==
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__TOC__
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[[4hnj]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4HNJ OCA].
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Fisher, J C.]]
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[[Category: Fisher, J C]]
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[[Category: White, S W.]]
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[[Category: White, S W]]
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[[Category: Yun, M K.]]
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[[Category: Yun, M K]]
[[Category: Apoptosis regulation]]
[[Category: Apoptosis regulation]]
[[Category: Apoptosis-protein binding complex]]
[[Category: Apoptosis-protein binding complex]]

Revision as of 17:55, 24 December 2014

Crystallographic structure of BCL-xL domain-swapped dimer in complex with PUMA BH3 peptide at 2.9A resolution

4hnj, resolution 2.90Å

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