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| | ==Crystal structure of mouse BAX monomer== | | ==Crystal structure of mouse BAX monomer== |
| - | <StructureSection load='5w62' size='340' side='right' caption='[[5w62]], [[Resolution|resolution]] 2.20Å' scene=''> | + | <StructureSection load='5w62' size='340' side='right'caption='[[5w62]], [[Resolution|resolution]] 2.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5w62]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5W62 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5W62 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5w62]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5W62 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5W62 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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]] 2.196Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5w5x|5w5x]], [[5w5z|5w5z]], [[5w60|5w60]], [[5w61|5w61]], [[5w63|5w63]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Bax ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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=5w62 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5w62 OCA], [https://pdbe.org/5w62 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5w62 RCSB], [https://www.ebi.ac.uk/pdbsum/5w62 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5w62 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=5w62 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5w62 OCA], [http://pdbe.org/5w62 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5w62 RCSB], [http://www.ebi.ac.uk/pdbsum/5w62 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5w62 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/BAX_MOUSE BAX_MOUSE]] 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. BAX deficiency leads to lymphoid hyperplasia and male sterility, because of the cessation of sperm production.<ref>PMID:8358790</ref> <ref>PMID:21060336</ref> | + | [https://www.uniprot.org/uniprot/BAX_MOUSE BAX_MOUSE] 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. BAX deficiency leads to lymphoid hyperplasia and male sterility, because of the cessation of sperm production.<ref>PMID:8358790</ref> <ref>PMID:21060336</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: Lk3 transgenic mice]] | + | [[Category: Large Structures]] |
| - | [[Category: Colman, P M]] | + | [[Category: Mus musculus]] |
| - | [[Category: Czabotar, P E]] | + | [[Category: Colman PM]] |
| - | [[Category: Luo, C S]] | + | [[Category: Czabotar PE]] |
| - | [[Category: Robin, A Y]] | + | [[Category: Luo CS]] |
| - | [[Category: Apoptosis]] | + | [[Category: Robin AY]] |
| - | [[Category: Bax]]
| + | |
| - | [[Category: Monomer]]
| + | |
| - | [[Category: Mouse]]
| + | |
| Structural highlights
Function
BAX_MOUSE 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. BAX deficiency leads to lymphoid hyperplasia and male sterility, because of the cessation of sperm production.[1] [2]
Publication Abstract from PubMed
BAX and BAK are essential mediators of intrinsic apoptosis that permeabilize the mitochondrial outer membrane. BAX activation requires its translocation from cytosol to mitochondria where conformational changes cause its oligomerization. To better understand the critical step of translocation, we examined its blockade by mutation near the C terminus (P168G) or by antibody binding near the N terminus. Similarities in the crystal structures of wild-type and BAX P168G but significant other differences suggest that cytosolic BAX exists as an ensemble of conformers, and that the distribution of conformers within the ensemble determines the different functions of wild-type and mutant proteins. We also describe the structure of BAX in complex with an antibody, 3C10, that inhibits cytosolic BAX by limiting exposure of the membrane-associating helix alpha9, as does the P168G mutation. Our data for both means of BAX inhibition argue for an allosteric model of BAX regulation that derives from properties of the ensemble of conformers.
Ensemble Properties of Bax Determine Its Function.,Robin AY, Iyer S, Birkinshaw RW, Sandow J, Wardak A, Luo CS, Shi M, Webb AI, Czabotar PE, Kluck RM, Colman PM Structure. 2018 Aug 4. pii: S0969-2126(18)30252-1. doi:, 10.1016/j.str.2018.07.006. PMID:30122452[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Oltvai ZN, Milliman CL, Korsmeyer SJ. Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death. Cell. 1993 Aug 27;74(4):609-19. PMID:8358790
- ↑ Ku B, Liang C, Jung JU, Oh BH. Evidence that inhibition of BAX activation by BCL-2 involves its tight and preferential interaction with the BH3 domain of BAX. Cell Res. 2010 Nov 9. PMID:21060336 doi:10.1038/cr.2010.149
- ↑ Robin AY, Iyer S, Birkinshaw RW, Sandow J, Wardak A, Luo CS, Shi M, Webb AI, Czabotar PE, Kluck RM, Colman PM. Ensemble Properties of Bax Determine Its Function. Structure. 2018 Aug 4. pii: S0969-2126(18)30252-1. doi:, 10.1016/j.str.2018.07.006. PMID:30122452 doi:http://dx.doi.org/10.1016/j.str.2018.07.006
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