4tx5
From Proteopedia
(Difference between revisions)
| Line 1: | Line 1: | ||
| - | ''' | + | ==Crystal structure of Smac-DIABLO (in space group P65)== |
| + | <StructureSection load='4tx5' size='340' side='right' caption='[[4tx5]], [[Resolution|resolution]] 1.80Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[4tx5]] is a 2 chain structure. 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> | ||
| + | </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> | ||
| + | <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://www.rcsb.org/pdb/explore.do?structureId=4tx5 RCSB], [http://www.ebi.ac.uk/pdbsum/4tx5 PDBsum]</span></td></tr> | ||
| + | </table> | ||
| + | == 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> | ||
| + | == 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> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == 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 | + | 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<ref>PMID:25650938</ref> |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | + | == References == | |
| - | [[Category: | + | <references/> |
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Cossu, F]] | ||
| + | [[Category: Mastangelo, E]] | ||
[[Category: Milani, M]] | [[Category: Milani, M]] | ||
| - | [[Category: | + | [[Category: Apoptosis]] |
| - | [[Category: | + | [[Category: Smac-diablo]] |
Revision as of 13:15, 15 July 2015
Crystal structure of Smac-DIABLO (in space group P65)
| |||||||||||
