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| ==Bax domain swapped dimer in complex with BidBH3== | | ==Bax domain swapped dimer in complex with BidBH3== |
| <StructureSection load='4bd2' size='340' side='right' caption='[[4bd2]], [[Resolution|resolution]] 2.21Å' scene=''> | | <StructureSection load='4bd2' size='340' side='right'caption='[[4bd2]], [[Resolution|resolution]] 2.21Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
| <table><tr><td colspan='2'>[[4bd2]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BD2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4BD2 FirstGlance]. <br> | | <table><tr><td colspan='2'>[[4bd2]] 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=4BD2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4BD2 FirstGlance]. <br> |
| </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4bd6|4bd6]], [[4bd7|4bd7]], [[4bd8|4bd8]], [[4bdu|4bdu]]</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]] 2.206Å</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=4bd2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bd2 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4bd2 RCSB], [http://www.ebi.ac.uk/pdbsum/4bd2 PDBsum]</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=4bd2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bd2 OCA], [https://pdbe.org/4bd2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4bd2 RCSB], [https://www.ebi.ac.uk/pdbsum/4bd2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4bd2 ProSAT]</span></td></tr> |
| </table> | | </table> |
| == Function == | | == Function == |
| [[http://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> [[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/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> |
| <div style="background-color:#fffaf0;">
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| == Publication Abstract from PubMed ==
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| In stressed cells, apoptosis ensues when Bcl-2 family members Bax or Bak oligomerize and permeabilize the mitochondrial outer membrane. Certain BH3-only relatives can directly activate them to mediate this pivotal, poorly understood step. To clarify the conformational changes that induce Bax oligomerization, we determined crystal structures of BaxDeltaC21 treated with detergents and BH3 peptides. The peptides bound the Bax canonical surface groove but, unlike their complexes with prosurvival relatives, dissociated Bax into two domains. The structures define the sequence signature of activator BH3 domains and reveal how they can activate Bax via its groove by favoring release of its BH3 domain. Furthermore, Bax helices alpha2-alpha5 alone adopted a symmetric homodimer structure, supporting the proposal that two Bax molecules insert their BH3 domain into each other's surface groove to nucleate oligomerization. A planar lipophilic surface on this homodimer may engage the membrane. Our results thus define critical Bax transitions toward apoptosis.
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| Bax Crystal Structures Reveal How BH3 Domains Activate Bax and Nucleate Its Oligomerization to Induce Apoptosis.,Czabotar PE, Westphal D, Dewson G, Ma S, Hockings C, Fairlie WD, Lee EF, Yao S, Robin AY, Smith BJ, Huang DC, Kluck RM, Adams JM, Colman PM Cell. 2013 Jan 31;152(3):519-31. doi: 10.1016/j.cell.2012.12.031. PMID:23374347<ref>PMID:23374347</ref>
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| From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| | ==See Also== |
| </div>
| | *[[B-cell lymphoma proteins 3D structures|B-cell lymphoma proteins 3D structures]] |
| == References == | | == References == |
| <references/> | | <references/> |
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| </StructureSection> | | </StructureSection> |
| [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| [[Category: Adams, J M]] | | [[Category: Large Structures]] |
| [[Category: Colman, P M]] | | [[Category: Adams JM]] |
| [[Category: Czabotar, P E]] | | [[Category: Colman PM]] |
| [[Category: Westphal, D]] | | [[Category: Czabotar PE]] |
| [[Category: Apoptosis]] | | [[Category: Westphal D]] |
| [[Category: Bcl-2 family]]
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| [[Category: Programmed cell death]]
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