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| | <StructureSection load='4qvf' size='340' side='right'caption='[[4qvf]], [[Resolution|resolution]] 1.53Å' scene=''> | | <StructureSection load='4qvf' size='340' side='right'caption='[[4qvf]], [[Resolution|resolution]] 1.53Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4qvf]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4QVF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4QVF FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4qvf]] is a 2 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=4QVF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4QVF FirstGlance]. <br> |
| - | </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]], [[4qve|4qve]]</div></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]] 1.531Å</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=4qvf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qvf OCA], [https://pdbe.org/4qvf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4qvf RCSB], [https://www.ebi.ac.uk/pdbsum/4qvf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4qvf ProSAT]</span></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=4qvf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qvf OCA], [https://pdbe.org/4qvf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4qvf RCSB], [https://www.ebi.ac.uk/pdbsum/4qvf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4qvf ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == 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> [[https://www.uniprot.org/uniprot/B2L11_HUMAN B2L11_HUMAN]] Induces apoptosis and anoikis. Isoform BimL is more potent than isoform BimEL. Isoform Bim-alpha1, isoform Bim-alpha2 and isoform Bim-alpha3 induce apoptosis, although less potent than isoform BimEL, isoform BimL and isoform BimS. Isoform Bim-gamma induces apoptosis. Isoform Bim-alpha3 induces apoptosis possibly through a caspase-mediated pathway. Isoform BimAC and isoform BimABC lack the ability to induce apoptosis.<ref>PMID:9430630</ref> <ref>PMID:11734221</ref> <ref>PMID:12019181</ref> <ref>PMID:11997495</ref> <ref>PMID:15147734</ref> <ref>PMID:15486195</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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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Sreekanth, R]] | + | [[Category: Sreekanth R]] |
| - | [[Category: Yoon, H S]] | + | [[Category: Yoon HS]] |
| - | [[Category: Anti-apoptotic]]
| + | |
| - | [[Category: Apoptosis]]
| + | |
| - | [[Category: Bcl-2 like]]
| + | |
| - | [[Category: Bh3 binding]]
| + | |
| - | [[Category: Bim bh3]]
| + | |
| - | [[Category: Heterodimer]]
| + | |
| - | [[Category: Protein-peptide complex]]
| + | |
| 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
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[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, 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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