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| | <StructureSection load='4qve' size='340' side='right'caption='[[4qve]], [[Resolution|resolution]] 2.05Å' scene=''> | | <StructureSection load='4qve' size='340' side='right'caption='[[4qve]], [[Resolution|resolution]] 2.05Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4qve]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4QVE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4QVE FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4qve]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4QVE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4QVE FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=IMD:IMIDAZOLE'>IMD</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IMD:IMIDAZOLE'>IMD</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1maz|1maz]], [[4qvf|4qvf]]</td></tr> | + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1maz|1maz]], [[4qvf|4qvf]]</div></td></tr> |
| - | <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 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=4qve FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qve OCA], [https://pdbe.org/4qve PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4qve RCSB], [https://www.ebi.ac.uk/pdbsum/4qve PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4qve 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=4qve FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qve OCA], [http://pdbe.org/4qve PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4qve RCSB], [http://www.ebi.ac.uk/pdbsum/4qve PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4qve 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> [[http://www.uniprot.org/uniprot/BID_HUMAN BID_HUMAN]] The major proteolytic product p15 BID allows the release of cytochrome c (By similarity). Isoform 1, isoform 2 and isoform 4 induce ICE-like proteases and apoptosis. Isoform 3 does not induce apoptosis. Counters the protective effect of Bcl-2.<ref>PMID:14583606</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> [[https://www.uniprot.org/uniprot/BID_HUMAN BID_HUMAN]] The major proteolytic product p15 BID allows the release of cytochrome c (By similarity). Isoform 1, isoform 2 and isoform 4 induce ICE-like proteases and apoptosis. Isoform 3 does not induce apoptosis. Counters the protective effect of Bcl-2.<ref>PMID:14583606</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| | [[Category: Sreekanth, R]] | | [[Category: Sreekanth, R]] |
| 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] [BID_HUMAN] The major proteolytic product p15 BID allows the release of cytochrome c (By similarity). Isoform 1, isoform 2 and isoform 4 induce ICE-like proteases and apoptosis. Isoform 3 does not induce apoptosis. Counters the protective effect of Bcl-2.[5]
Publication Abstract from PubMed
Apoptosis or programmed cell death is a regulatory process in cells in response to stimuli perturbing physiological conditions. The Bcl-2 family of proteins plays an important role in regulating homeostasis during apoptosis. In the process, the molecular interactions among the three members of this family, the pro-apoptotic, anti-apoptotic and BH3-only proteins at the mitochondrial outer membrane define the fate of a cell. Here, we report the crystal structures of the human anti-apoptotic protein Bcl-XL in complex with BH3-only BIDBH3 and BIMBH3 peptides determined at 2.0 A and 1.5 A resolution, respectively. The BH3 peptides bind to the canonical hydrophobic pocket in Bcl-XL and adopt an alpha helical conformation in the bound form. Despite a similar structural fold, a comparison with other BH3 complexes revealed structural differences due to their sequence variations. In the Bcl-XL -BIDBH3 complex we observed a large pocket, in comparison with other BH3 complexes, lined by residues from helices alpha1, alpha2, alpha3, and alpha5 located adjacent to the canonical hydrophobic pocket. These results suggest that there are differences in the mode of interactions by the BH3 peptides that may translate into functional differences in apoptotic regulation. Proteins 2015. (c) 2015 Wiley Periodicals, Inc.
Bh3 induced conformational changes in Bcl-X revealed by crystal structure and comparative analysis.,Rajan S, Choi M, Baek K, Yoon HS Proteins. 2015 Apr 23. doi: 10.1002/prot.24816. PMID:25907960[6]
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
- ↑ Renshaw SA, Dempsey CE, Barnes FA, Bagstaff SM, Dower SK, Bingle CD, Whyte MK. Three novel Bid proteins generated by alternative splicing of the human Bid gene. J Biol Chem. 2004 Jan 23;279(4):2846-55. Epub 2003 Oct 28. PMID:14583606 doi:http://dx.doi.org/10.1074/jbc.M309769200
- ↑ Rajan S, Choi M, Baek K, Yoon HS. Bh3 induced conformational changes in Bcl-X revealed by crystal structure and comparative analysis. Proteins. 2015 Apr 23. doi: 10.1002/prot.24816. PMID:25907960 doi:http://dx.doi.org/10.1002/prot.24816
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