2k7w
From Proteopedia
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- | [[Image:2k7w.png|left|200px]] | ||
- | + | ==BAX Activation is Initiated at a Novel Interaction Site== | |
+ | <StructureSection load='2k7w' size='340' side='right'caption='[[2k7w]]' scene=''> | ||
+ | == Structural highlights == | ||
+ | <table><tr><td colspan='2'>[[2k7w]] is a 2 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=2K7W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2K7W FirstGlance]. <br> | ||
+ | </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'>[https://proteopedia.org/fgij/fg.htm?mol=2k7w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2k7w OCA], [https://pdbe.org/2k7w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2k7w RCSB], [https://www.ebi.ac.uk/pdbsum/2k7w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2k7w ProSAT]</span></td></tr> | ||
+ | </table> | ||
+ | == Function == | ||
+ | [https://www.uniprot.org/uniprot/BAX_HUMAN BAX_HUMAN] Accelerates programmed cell death by binding to, and antagonizing the apoptosis repressor BCL2 or its adenovirus homolog E1B 19k protein. Under stress conditions, undergoes a conformation change that causes translocation to the mitochondrion membrane, leading to the release of cytochrome c that then triggers apoptosis. Promotes activation of CASP3, and thereby apoptosis.<ref>PMID:8358790</ref> <ref>PMID:10772918</ref> <ref>PMID:8521816</ref> <ref>PMID:16113678</ref> <ref>PMID:18948948</ref> <ref>PMID:21199865</ref> | ||
+ | == Evolutionary Conservation == | ||
+ | [[Image:Consurf_key_small.gif|200px|right]] | ||
+ | Check<jmol> | ||
+ | <jmolCheckbox> | ||
+ | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/k7/2k7w_consurf.spt"</scriptWhenChecked> | ||
+ | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | ||
+ | <text>to colour the structure by Evolutionary Conservation</text> | ||
+ | </jmolCheckbox> | ||
+ | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2k7w ConSurf]. | ||
+ | <div style="clear:both"></div> | ||
+ | <div style="background-color:#fffaf0;"> | ||
+ | == Publication Abstract from PubMed == | ||
+ | BAX is a pro-apoptotic protein of the BCL-2 family that is stationed in the cytosol until activated by a diversity of stress stimuli to induce cell death. Anti-apoptotic proteins such as BCL-2 counteract BAX-mediated cell death. Although an interaction site that confers survival functionality has been defined for anti-apoptotic proteins, an activation site has not been identified for BAX, rendering its explicit trigger mechanism unknown. We previously developed stabilized alpha-helix of BCL-2 domains (SAHBs) that directly initiate BAX-mediated mitochondrial apoptosis. Here we demonstrate by NMR analysis that BIM SAHB binds BAX at an interaction site that is distinct from the canonical binding groove characterized for anti-apoptotic proteins. The specificity of the human BIM-SAHB-BAX interaction is highlighted by point mutagenesis that disrupts functional activity, confirming that BAX activation is initiated at this novel structural location. Thus, we have now defined a BAX interaction site for direct activation, establishing a new target for therapeutic modulation of apoptosis. | ||
- | + | BAX activation is initiated at a novel interaction site.,Gavathiotis E, Suzuki M, Davis ML, Pitter K, Bird GH, Katz SG, Tu HC, Kim H, Cheng EH, Tjandra N, Walensky LD Nature. 2008 Oct 23;455(7216):1076-81. PMID:18948948<ref>PMID:18948948</ref> | |
- | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
+ | </div> | ||
+ | <div class="pdbe-citations 2k7w" style="background-color:#fffaf0;"></div> | ||
- | == | + | ==See Also== |
- | [[ | + | *[[B-cell lymphoma proteins 3D structures|B-cell lymphoma proteins 3D structures]] |
- | + | == References == | |
- | == | + | <references/> |
- | < | + | __TOC__ |
+ | </StructureSection> | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
- | [[Category: Bird | + | [[Category: Large Structures]] |
- | [[Category: Cheng | + | [[Category: Bird GH]] |
- | [[Category: Davis | + | [[Category: Cheng EH]] |
- | [[Category: Gavathiotis | + | [[Category: Davis ML]] |
- | [[Category: Katz | + | [[Category: Gavathiotis E]] |
- | [[Category: Kim | + | [[Category: Katz SG]] |
- | [[Category: Pitter | + | [[Category: Kim H]] |
- | [[Category: Suzuki | + | [[Category: Pitter K]] |
- | [[Category: Tjandra | + | [[Category: Suzuki M]] |
- | [[Category: Tu | + | [[Category: Tjandra N]] |
- | [[Category: Walensky | + | [[Category: Tu HC]] |
- | + | [[Category: Walensky LD]] | |
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Current revision
BAX Activation is Initiated at a Novel Interaction Site
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Categories: Homo sapiens | Large Structures | Bird GH | Cheng EH | Davis ML | Gavathiotis E | Katz SG | Kim H | Pitter K | Suzuki M | Tjandra N | Tu HC | Walensky LD