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| | <StructureSection load='2yv6' size='340' side='right'caption='[[2yv6]], [[Resolution|resolution]] 2.50Å' scene=''> | | <StructureSection load='2yv6' size='340' side='right'caption='[[2yv6]], [[Resolution|resolution]] 2.50Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2yv6]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2YV6 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=2YV6 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2yv6]] is a 1 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=2YV6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2YV6 FirstGlance]. <br> |
| - | </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> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=2yv6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2yv6 OCA], [http://pdbe.org/2yv6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2yv6 RCSB], [http://www.ebi.ac.uk/pdbsum/2yv6 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2yv6 ProSAT], [http://www.topsan.org/Proteins/RSGI/2yv6 TOPSAN]</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=2yv6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2yv6 OCA], [https://pdbe.org/2yv6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2yv6 RCSB], [https://www.ebi.ac.uk/pdbsum/2yv6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2yv6 ProSAT], [https://www.topsan.org/Proteins/RSGI/2yv6 TOPSAN]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/BAK_HUMAN BAK_HUMAN]] In the presence of an appropriate stimulus, accelerates programmed cell death by binding to, and antagonizing the anti-apoptotic action of BCL2 or its adenovirus homolog E1B 19k protein. Low micromolar levels of zinc ions inhibit the promotion of apoptosis.<ref>PMID:8521816</ref> <ref>PMID:17157251</ref> | + | [https://www.uniprot.org/uniprot/BAK_HUMAN BAK_HUMAN] In the presence of an appropriate stimulus, accelerates programmed cell death by binding to, and antagonizing the anti-apoptotic action of BCL2 or its adenovirus homolog E1B 19k protein. Low micromolar levels of zinc ions inhibit the promotion of apoptosis.<ref>PMID:8521816</ref> <ref>PMID:17157251</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | <jmolCheckbox> | | <jmolCheckbox> |
| | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/yv/2yv6_consurf.spt"</scriptWhenChecked> | | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/yv/2yv6_consurf.spt"</scriptWhenChecked> |
| - | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
| | </jmolCheckbox> | | </jmolCheckbox> |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Kishishita, S]] | + | [[Category: Kishishita S]] |
| - | [[Category: Murayama, K]] | + | [[Category: Murayama K]] |
| - | [[Category: Structural genomic]]
| + | [[Category: Shirouzu M]] |
| - | [[Category: Shirouzu, M]] | + | [[Category: Takemoto C]] |
| - | [[Category: Takemoto, C]] | + | [[Category: Terada T]] |
| - | [[Category: Terada, T]] | + | [[Category: Wang H]] |
| - | [[Category: Wang, H]] | + | |
| - | [[Category: Apoptosis]]
| + | |
| - | [[Category: Bcl domain]]
| + | |
| - | [[Category: National project on protein structural and functional analyse]]
| + | |
| - | [[Category: Nppsfa]]
| + | |
| - | [[Category: Rsgi]]
| + | |
| Structural highlights
Function
BAK_HUMAN In the presence of an appropriate stimulus, accelerates programmed cell death by binding to, and antagonizing the anti-apoptotic action of BCL2 or its adenovirus homolog E1B 19k protein. Low micromolar levels of zinc ions inhibit the promotion of apoptosis.[1] [2]
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
Interactions of Bcl-2 family proteins play a regulatory role in mitochondrial apoptosis. The pro-apoptotic protein Bak resides in the outer mitochondrial membrane, and the formation of Bak homo- or heterodimers is involved in the regulation of apoptosis. The previously reported structure of the human Bak protein (residues Glu16-Gly186) revealed that a zinc ion was coordinated with two pairs of Asp160 and His164 residues from the symmetry-related molecules. This zinc-dependent homodimer was regarded as an anti-apoptotic dimer. In the present study, we determined the crystal structure of the human Bak residues Ser23-Asn185 at 2.5A, and found a distinct type of homodimerization through Cys166 disulfide bridging between the symmetry-related molecules. In the two modes of homodimerization, the molecular interfaces are completely different. In the membrane-targeted model of the S-S bridged dimer, the BH3 motifs are too close to the membrane to interact directly with the anti-apoptotic relatives, such as Bcl-x(L). Therefore, the Bak dimer structure reported here may represent a pro-apoptotic mode under oxidized conditions.
Novel dimerization mode of the human Bcl-2 family protein Bak, a mitochondrial apoptosis regulator.,Wang H, Takemoto C, Akasaka R, Uchikubo-Kamo T, Kishishita S, Murayama K, Terada T, Chen L, Liu ZJ, Wang BC, Sugano S, Tanaka A, Inoue M, Kigawa T, Shirouzu M, Yokoyama S J Struct Biol. 2009 Apr;166(1):32-7. Epub 2008 Dec 24. PMID:19135534[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Chittenden T, Flemington C, Houghton AB, Ebb RG, Gallo GJ, Elangovan B, Chinnadurai G, Lutz RJ. A conserved domain in Bak, distinct from BH1 and BH2, mediates cell death and protein binding functions. EMBO J. 1995 Nov 15;14(22):5589-96. PMID:8521816
- ↑ Moldoveanu T, Liu Q, Tocilj A, Watson M, Shore G, Gehring K. The X-ray structure of a BAK homodimer reveals an inhibitory zinc binding site. Mol Cell. 2006 Dec 8;24(5):677-88. PMID:17157251 doi:10.1016/j.molcel.2006.10.014
- ↑ Wang H, Takemoto C, Akasaka R, Uchikubo-Kamo T, Kishishita S, Murayama K, Terada T, Chen L, Liu ZJ, Wang BC, Sugano S, Tanaka A, Inoue M, Kigawa T, Shirouzu M, Yokoyama S. Novel dimerization mode of the human Bcl-2 family protein Bak, a mitochondrial apoptosis regulator. J Struct Biol. 2009 Apr;166(1):32-7. Epub 2008 Dec 24. PMID:19135534 doi:10.1016/j.jsb.2008.12.003
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