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| | ==THE STRUCTURE OF BCL-W REVEALS A ROLE FOR THE C-TERMINAL RESIDUES IN MODULATING BIOLOGICAL ACTIVITY== | | ==THE STRUCTURE OF BCL-W REVEALS A ROLE FOR THE C-TERMINAL RESIDUES IN MODULATING BIOLOGICAL ACTIVITY== |
| - | <StructureSection load='1o0l' size='340' side='right'caption='[[1o0l]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='1o0l' size='340' side='right'caption='[[1o0l]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1o0l]] is a 1 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=1O0L OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=1O0L FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1o0l]] is a 1 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=1O0L OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1O0L FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BCL2L2 OR BCLW OR KIAA0271 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=1o0l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1o0l OCA], [http://pdbe.org/1o0l PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1o0l RCSB], [http://www.ebi.ac.uk/pdbsum/1o0l PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1o0l 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=1o0l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1o0l OCA], [https://pdbe.org/1o0l PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1o0l RCSB], [https://www.ebi.ac.uk/pdbsum/1o0l PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1o0l ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/B2CL2_HUMAN B2CL2_HUMAN]] Promotes cell survival. Blocks dexamethasone-induced apoptosis. Mediates survival of postmitotic Sertoli cells by suppressing death-promoting activity of BAX.<ref>PMID:8761287</ref> | + | [https://www.uniprot.org/uniprot/B2CL2_HUMAN B2CL2_HUMAN] Promotes cell survival. Blocks dexamethasone-induced apoptosis. Mediates survival of postmitotic Sertoli cells by suppressing death-promoting activity of BAX.<ref>PMID:8761287</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Day, C L]] | + | [[Category: Day CL]] |
| - | [[Category: Harrison, P J]] | + | [[Category: Harrison PJ]] |
| - | [[Category: Hinds, M G]] | + | [[Category: Hinds MG]] |
| - | [[Category: Huang, D C.S]] | + | [[Category: Huang DCS]] |
| - | [[Category: Lackmann, M]] | + | [[Category: Lackmann M]] |
| - | [[Category: Skea, G L]] | + | [[Category: Skea GL]] |
| - | [[Category: Apoptosis]]
| + | |
| - | [[Category: Bcl-2]]
| + | |
| - | [[Category: Bh3]]
| + | |
| - | [[Category: Binding groove]]
| + | |
| - | [[Category: Helical bundle]]
| + | |
| Structural highlights
Function
B2CL2_HUMAN Promotes cell survival. Blocks dexamethasone-induced apoptosis. Mediates survival of postmitotic Sertoli cells by suppressing death-promoting activity of BAX.[1]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Pro-survival Bcl-2-related proteins, critical regulators of apoptosis, contain a hydrophobic groove targeted for binding by the BH3 domain of the pro-apoptotic BH3-only proteins. The solution structure of the pro-survival protein Bcl-w, presented here, reveals that the binding groove is not freely accessible as predicted by previous structures of pro-survival Bcl-2-like molecules. Unexpectedly, the groove appears to be occluded by the C-terminal residues. Binding and kinetic data suggest that the C-terminal residues of Bcl-w and Bcl-x(L) modulate pro-survival activity by regulating ligand access to the groove. Binding of the BH3-only proteins, critical for cell death initiation, is likely to displace the hydrophobic C-terminal region of Bcl-w and Bcl-x(L). Moreover, Bcl-w does not act only by sequestering the BH3-only proteins. There fore, pro-survival Bcl-2-like molecules probably control the activation of downstream effectors by a mechanism that remains to be elucidated.
The structure of Bcl-w reveals a role for the C-terminal residues in modulating biological activity.,Hinds MG, Lackmann M, Skea GL, Harrison PJ, Huang DC, Day CL EMBO J. 2003 Apr 1;22(7):1497-507. PMID:12660157[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Gibson L, Holmgreen SP, Huang DC, Bernard O, Copeland NG, Jenkins NA, Sutherland GR, Baker E, Adams JM, Cory S. bcl-w, a novel member of the bcl-2 family, promotes cell survival. Oncogene. 1996 Aug 15;13(4):665-75. PMID:8761287
- ↑ Hinds MG, Lackmann M, Skea GL, Harrison PJ, Huang DC, Day CL. The structure of Bcl-w reveals a role for the C-terminal residues in modulating biological activity. EMBO J. 2003 Apr 1;22(7):1497-507. PMID:12660157 doi:10.1093/emboj/cdg144
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