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| | ==Crystal structure of Bcl-xL hexamer== | | ==Crystal structure of Bcl-xL hexamer== |
| - | <StructureSection load='4ppi' size='340' side='right' caption='[[4ppi]], [[Resolution|resolution]] 2.85Å' scene=''> | + | <StructureSection load='4ppi' size='340' side='right'caption='[[4ppi]], [[Resolution|resolution]] 2.85Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4ppi]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4PPI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4PPI FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4ppi]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4PPI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4PPI FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.851Å</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=4ppi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ppi OCA], [http://pdbe.org/4ppi PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ppi RCSB], [http://www.ebi.ac.uk/pdbsum/4ppi PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ppi ProSAT]</span></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</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=4ppi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ppi OCA], [https://pdbe.org/4ppi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ppi RCSB], [https://www.ebi.ac.uk/pdbsum/4ppi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ppi ProSAT]</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> | + | [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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 4ppi" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 4ppi" 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: Sreekanth, R]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Yoon, H S]] | + | [[Category: Large Structures]] |
| - | [[Category: 3d domain swap]] | + | [[Category: Sreekanth R]] |
| - | [[Category: Anti-apoptotic]] | + | [[Category: Yoon HS]] |
| - | [[Category: Apoptosis]]
| + | |
| - | [[Category: Bcl-2 family]]
| + | |
| Structural highlights
Function
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.[1] [2] Isoform Bcl-X(S) promotes apoptosis.[3] [4]
Publication Abstract from PubMed
Bcl-2 family proteins are key regulators for cellular homeostasis in response to apoptotic stimuli. Bcl-xL, an antiapoptotic Bcl-2 family member, undergoes conformational transitions, which leads to two conformational states: the cytoplasmic and membrane-bound. Here we present the crystal and small-angle X-ray scattering (SAXS) structures of Bcl-xL treated with the mild detergent n-Octyl beta-D-Maltoside (OM). The detergent-treated Bcl-xL forms a dimer through three-dimensional domain swapping (3DDS) by swapping helices alpha6-alpha8 between two monomers. Unlike Bax, a proapoptotic member of the Bcl-2 family, Bcl-xL is not converted to 3DDS homodimer upon binding BH3 peptides and ABT-737, a BH3 mimetic drug. We also designed Bcl-xL mutants which cannot dimerize and show that these mutants reduced mitochondrial calcium uptake in MEF cells. This illustrates the structural plasticity in Bcl-xL providing hints toward the probable molecular mechanism for Bcl-xL to play a regulatory role in mitochondrial calcium ion transport.
Structural transition in Bcl-xL and its potential association with mitochondrial calcium ion transport.,Rajan S, Choi M, Nguyen QT, Ye H, Liu W, Toh HT, Kang C, Kamariah N, Li C, Huang H, White C, Baek K, Gruber G, Yoon HS Sci Rep. 2015 May 29;5:10609. doi: 10.1038/srep10609. PMID:26023881[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Terrano DT, Upreti M, Chambers TC. Cyclin-dependent kinase 1-mediated Bcl-xL/Bcl-2 phosphorylation acts as a functional link coupling mitotic arrest and apoptosis. Mol Cell Biol. 2010 Feb;30(3):640-56. doi: 10.1128/MCB.00882-09. Epub 2009 Nov, 16. PMID:19917720 doi:10.1128/MCB.00882-09
- ↑ Wang J, Beauchemin M, Bertrand R. Bcl-xL phosphorylation at Ser49 by polo kinase 3 during cell cycle progression and checkpoints. Cell Signal. 2011 Dec;23(12):2030-8. doi: 10.1016/j.cellsig.2011.07.017. Epub, 2011 Aug 5. PMID:21840391 doi:10.1016/j.cellsig.2011.07.017
- ↑ Terrano DT, Upreti M, Chambers TC. Cyclin-dependent kinase 1-mediated Bcl-xL/Bcl-2 phosphorylation acts as a functional link coupling mitotic arrest and apoptosis. Mol Cell Biol. 2010 Feb;30(3):640-56. doi: 10.1128/MCB.00882-09. Epub 2009 Nov, 16. PMID:19917720 doi:10.1128/MCB.00882-09
- ↑ Wang J, Beauchemin M, Bertrand R. Bcl-xL phosphorylation at Ser49 by polo kinase 3 during cell cycle progression and checkpoints. Cell Signal. 2011 Dec;23(12):2030-8. doi: 10.1016/j.cellsig.2011.07.017. Epub, 2011 Aug 5. PMID:21840391 doi:10.1016/j.cellsig.2011.07.017
- ↑ Rajan S, Choi M, Nguyen QT, Ye H, Liu W, Toh HT, Kang C, Kamariah N, Li C, Huang H, White C, Baek K, Gruber G, Yoon HS. Structural transition in Bcl-xL and its potential association with mitochondrial calcium ion transport. Sci Rep. 2015 May 29;5:10609. doi: 10.1038/srep10609. PMID:26023881 doi:http://dx.doi.org/10.1038/srep10609
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