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| | <StructureSection load='4tx5' size='340' side='right'caption='[[4tx5]], [[Resolution|resolution]] 1.80Å' scene=''> | | <StructureSection load='4tx5' size='340' side='right'caption='[[4tx5]], [[Resolution|resolution]] 1.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4tx5]] is a 2 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=4TX5 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4TX5 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4tx5]] 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=4TX5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4TX5 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DIABLO, SMAC ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4tx5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4tx5 OCA], [https://pdbe.org/4tx5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4tx5 RCSB], [https://www.ebi.ac.uk/pdbsum/4tx5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4tx5 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=4tx5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4tx5 OCA], [http://pdbe.org/4tx5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4tx5 RCSB], [http://www.ebi.ac.uk/pdbsum/4tx5 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4tx5 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/DBLOH_HUMAN DBLOH_HUMAN]] Defects in DIABLO are the cause of deafness autosomal dominant type 64 (DFNA64) [MIM:[http://omim.org/entry/614152 614152]]. DFNA64 is a form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information.<ref>PMID:21722859</ref> | + | [https://www.uniprot.org/uniprot/DBLOH_HUMAN DBLOH_HUMAN] Defects in DIABLO are the cause of deafness autosomal dominant type 64 (DFNA64) [MIM:[https://omim.org/entry/614152 614152]. DFNA64 is a form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information.<ref>PMID:21722859</ref> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/DBLOH_HUMAN DBLOH_HUMAN]] Promotes apoptosis by activating caspases in the cytochrome c/Apaf-1/caspase-9 pathway. Acts by opposing the inhibitory activity of inhibitor of apoptosis proteins (IAP). Inhibits the activity of BIRC6/bruce by inhibiting its binding to caspases. Isoform 3 attenuates the stability and apoptosis-inhibiting activity of XIAP/BIRC4 by promoting XIAP/BIRC4 ubiquitination and degradation through the ubiquitin-proteasome pathway. Isoform 3 also disrupts XIAP/BIRC4 interacting with processed caspase-9 and promotes caspase-3 activation. Isoform 1 is defective in the capacity to down-regulate the XIAP/BIRC4 abundance.<ref>PMID:10929711</ref> <ref>PMID:14523016</ref> <ref>PMID:15200957</ref> | + | [https://www.uniprot.org/uniprot/DBLOH_HUMAN DBLOH_HUMAN] Promotes apoptosis by activating caspases in the cytochrome c/Apaf-1/caspase-9 pathway. Acts by opposing the inhibitory activity of inhibitor of apoptosis proteins (IAP). Inhibits the activity of BIRC6/bruce by inhibiting its binding to caspases. Isoform 3 attenuates the stability and apoptosis-inhibiting activity of XIAP/BIRC4 by promoting XIAP/BIRC4 ubiquitination and degradation through the ubiquitin-proteasome pathway. Isoform 3 also disrupts XIAP/BIRC4 interacting with processed caspase-9 and promotes caspase-3 activation. Isoform 1 is defective in the capacity to down-regulate the XIAP/BIRC4 abundance.<ref>PMID:10929711</ref> <ref>PMID:14523016</ref> <ref>PMID:15200957</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: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Cossu, F]] | + | [[Category: Cossu F]] |
| - | [[Category: Mastangelo, E]] | + | [[Category: Mastangelo E]] |
| - | [[Category: Milani, M]] | + | [[Category: Milani M]] |
| - | [[Category: Apoptosis]]
| + | |
| - | [[Category: Smac-diablo]]
| + | |
| Structural highlights
Disease
DBLOH_HUMAN Defects in DIABLO are the cause of deafness autosomal dominant type 64 (DFNA64) [MIM:614152. DFNA64 is a form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information.[1]
Function
DBLOH_HUMAN Promotes apoptosis by activating caspases in the cytochrome c/Apaf-1/caspase-9 pathway. Acts by opposing the inhibitory activity of inhibitor of apoptosis proteins (IAP). Inhibits the activity of BIRC6/bruce by inhibiting its binding to caspases. Isoform 3 attenuates the stability and apoptosis-inhibiting activity of XIAP/BIRC4 by promoting XIAP/BIRC4 ubiquitination and degradation through the ubiquitin-proteasome pathway. Isoform 3 also disrupts XIAP/BIRC4 interacting with processed caspase-9 and promotes caspase-3 activation. Isoform 1 is defective in the capacity to down-regulate the XIAP/BIRC4 abundance.[2] [3] [4]
Publication Abstract from PubMed
Smac-DIABLO in its mature form (20.8 kDa) binds to baculoviral IAP repeat (BIR) domains of inhibitor of apoptosis proteins (IAPs) releasing their inhibitory effects on caspases, thus promoting cell death. Despite its apparent molecular mass ( approximately 100 kDa), Smac-DIABLO was held to be a dimer in solution, simultaneously targeting two distinct BIR domains. We report an extensive biophysical characterization of the protein alone and in complex with the X-linked IAP (XIAP)-BIR2-BIR3 domains. Our data show that Smac-DIABLO adopts a tetrameric assembly in solution and that the tetramer is able to bind two BIR2-BIR3 pairs of domains. Our small-angle x-ray scattering-based tetrameric model of Smac-DIABLO/BIR2-BIR3 highlights some conformational freedom of the complex that may be related to optimization of IAPs binding.
The activator of apoptosis Smac-DIABLO acts as a tetramer in solution.,Mastrangelo E, Vachette P, Cossu F, Malvezzi F, Bolognesi M, Milani M Biophys J. 2015 Feb 3;108(3):714-23. doi: 10.1016/j.bpj.2014.11.3471. PMID:25650938[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Cheng J, Zhu Y, He S, Lu Y, Chen J, Han B, Petrillo M, Wrzeszczynski KO, Yang S, Dai P, Zhai S, Han D, Zhang MQ, Li W, Liu X, Li H, Chen ZY, Yuan H. Functional mutation of SMAC/DIABLO, encoding a mitochondrial proapoptotic protein, causes human progressive hearing loss DFNA64. Am J Hum Genet. 2011 Jul 15;89(1):56-66. doi: 10.1016/j.ajhg.2011.05.027. Epub, 2011 Jun 30. PMID:21722859 doi:10.1016/j.ajhg.2011.05.027
- ↑ Du C, Fang M, Li Y, Li L, Wang X. Smac, a mitochondrial protein that promotes cytochrome c-dependent caspase activation by eliminating IAP inhibition. Cell. 2000 Jul 7;102(1):33-42. PMID:10929711
- ↑ Fu J, Jin Y, Arend LJ. Smac3, a novel Smac/DIABLO splicing variant, attenuates the stability and apoptosis-inhibiting activity of X-linked inhibitor of apoptosis protein. J Biol Chem. 2003 Dec 26;278(52):52660-72. Epub 2003 Sep 30. PMID:14523016 doi:10.1074/jbc.M308036200
- ↑ Bartke T, Pohl C, Pyrowolakis G, Jentsch S. Dual role of BRUCE as an antiapoptotic IAP and a chimeric E2/E3 ubiquitin ligase. Mol Cell. 2004 Jun 18;14(6):801-11. PMID:15200957 doi:10.1016/j.molcel.2004.05.018
- ↑ Mastrangelo E, Vachette P, Cossu F, Malvezzi F, Bolognesi M, Milani M. The activator of apoptosis Smac-DIABLO acts as a tetramer in solution. Biophys J. 2015 Feb 3;108(3):714-23. doi: 10.1016/j.bpj.2014.11.3471. PMID:25650938 doi:http://dx.doi.org/10.1016/j.bpj.2014.11.3471
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