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| | ==Solution structure of BCL-xL in complex with PUMA BH3 peptide== | | ==Solution structure of BCL-xL in complex with PUMA BH3 peptide== |
| - | <StructureSection load='2m04' size='340' side='right' caption='[[2m04]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='2m04' size='340' side='right'caption='[[2m04]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2m04]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2M04 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2M04 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2m04]] 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=2M04 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2M04 FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2m03|2m03]], [[4hnj|4hnj]]</td></tr> | + | </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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BCL2-like 1, BCL2L, BCL2L1, BCLX ([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'>[https://proteopedia.org/fgij/fg.htm?mol=2m04 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2m04 OCA], [https://pdbe.org/2m04 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2m04 RCSB], [https://www.ebi.ac.uk/pdbsum/2m04 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2m04 ProSAT]</span></td></tr> |
| - | <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=2m04 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2m04 OCA], [http://pdbe.org/2m04 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2m04 RCSB], [http://www.ebi.ac.uk/pdbsum/2m04 PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[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> [[http://www.uniprot.org/uniprot/BBC3_HUMAN BBC3_HUMAN]] Essential mediator of p53/TP53-dependent and p53/TP53-independent apoptosis. Functions by promoting partial unfolding of BCL2L1 and dissociation of BCL2L1 from p53/TP53. Regulates ER stress-induced neuronal apoptosis.<ref>PMID:11463391</ref> <ref>PMID:23340338</ref> | + | [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;">
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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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| - | 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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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | ==See Also== |
| - | </div>
| + | *[[B-cell lymphoma proteins 3D structures|B-cell lymphoma proteins 3D structures]] |
| - | <div class="pdbe-citations 2m04" style="background-color:#fffaf0;"></div>
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| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Follis, A Viacava]] | + | [[Category: Large Structures]] |
| - | [[Category: Kriwacki, R W]] | + | [[Category: Kriwacki RW]] |
| - | [[Category: Royappa, G]] | + | [[Category: Royappa G]] |
| - | [[Category: Apoptosis-protein binding complex]] | + | [[Category: Viacava Follis A]] |
| - | [[Category: Bcl-xl]]
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| - | [[Category: Puma]]
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