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| | ==Co-crystallization with conformation-specific designed ankyrin repeat proteins explains the conformational flexibility of BCL-W== | | ==Co-crystallization with conformation-specific designed ankyrin repeat proteins explains the conformational flexibility of BCL-W== |
| - | <StructureSection load='4k5b' size='340' side='right' caption='[[4k5b]], [[Resolution|resolution]] 1.85Å' scene=''> | + | <StructureSection load='4k5b' size='340' side='right'caption='[[4k5b]], [[Resolution|resolution]] 1.85Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4k5b]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_coli"_migula_1895 "bacillus coli" migula 1895] and [http://en.wikipedia.org/wiki/Bovin Bovin]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4K5B OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4K5B FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4k5b]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus] and [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4K5B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4K5B FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4k5a|4k5a]]</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]] 1.85Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BCL2L2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9913 BOVIN])</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=4k5b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4k5b OCA], [https://pdbe.org/4k5b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4k5b RCSB], [https://www.ebi.ac.uk/pdbsum/4k5b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4k5b 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=4k5b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4k5b OCA], [http://pdbe.org/4k5b PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4k5b RCSB], [http://www.ebi.ac.uk/pdbsum/4k5b PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4k5b ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/B2CL2_BOVIN B2CL2_BOVIN]] Promotes cell survival. Blocks dexamethasone-induced apoptosis. Mediates survival of postmitotic Sertoli cells by suppressing death-promoting activity of BAX (By similarity). | + | [https://www.uniprot.org/uniprot/B2CL2_BOVIN B2CL2_BOVIN] Promotes cell survival. Blocks dexamethasone-induced apoptosis. Mediates survival of postmitotic Sertoli cells by suppressing death-promoting activity of BAX (By similarity). |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | BCL-W is a member of the BCL-2 family of anti-apoptotic proteins. A key event in the regulation of apoptosis is the heterodimerization between anti-apoptotic and pro-apoptotic family members, which involves a conserved surface-exposed groove on the anti-apoptotic proteins. Crystal structures of the ligand binding-competent conformation exist for all anti-apoptotic family members, with the exception of BCL-W, due to the flexibility of the BCL-W groove region. Existing structures had suggested major deviations of the BCL-W groove region from the otherwise structurally highly related remaining anti-apoptotic family members. To capture its ligand binding-competent conformation by counteracting the conformational flexibility of the BCL-W groove, we had selected high-affinity groove-binding designed ankyrin repeat proteins (DARPins) using ribosome-display. We now determined two high-resolution crystal structures of human BCL-W in complex with different DARPins at a resolution of 1.5 and 1.85A, in which the structure of BCL-W is virtually identical, and in both structures BCL-W adopts a conformation extremely similar to the ligand-free conformation of its closest relative BCL-XL. However, distinct differences to all previous BCL-W structures are evident, notably in the ligand-binding region. We provide the first structural explanation for the conformational flexibility of the BCL-W groove region in comparison to other BCL-2 family members. Due to the importance of the anti-apoptotic BCL-2 family as drug targets, the presented crystal structure of ligand binding-competent BCL-W may serve as a valuable basis for structure-based drug design in the future and provides a missing piece for the structural characterization of this protein family.
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| - | Co-crystallization with conformation-specific designed ankyrin repeat proteins explains the conformational flexibility of BCL-W.,Schilling J, Schoppe J, Sauer E, Pluckthun A J Mol Biol. 2014 Apr 17. pii: S0022-2836(14)00194-6. doi:, 10.1016/j.jmb.2014.04.010. PMID:24747052<ref>PMID:24747052</ref>
| + | ==See Also== |
| - | | + | *[[B-cell lymphoma proteins 3D structures|B-cell lymphoma proteins 3D structures]] |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 4k5b" style="background-color:#fffaf0;"></div>
| + | |
| - | == References ==
| + | |
| - | <references/>
| + | |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Bacillus coli migula 1895]] | + | [[Category: Bos taurus]] |
| - | [[Category: Bovin]] | + | [[Category: Escherichia coli]] |
| - | [[Category: Plueckthun, A]] | + | [[Category: Large Structures]] |
| - | [[Category: Sauer, E]] | + | [[Category: Plueckthun A]] |
| - | [[Category: Schilling, J]] | + | [[Category: Sauer E]] |
| - | [[Category: Schoeppe, J]] | + | [[Category: Schilling J]] |
| - | [[Category: Anti-apoptotic bcl-2 family]]
| + | [[Category: Schoeppe J]] |
| - | [[Category: Apoptosis]]
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| - | [[Category: Bcl-w]]
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| - | [[Category: Crystal structure]]
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| - | [[Category: Darpin]]
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| - | [[Category: Ligand binding-competent conformation]]
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