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1xb1

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Revision as of 06:57, 18 April 2018

The Structure of the BIR domain of IAP-like protein 2

Structural highlights

1xb1 is a 12 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	1xb0
Gene:	BIRC8, ILP2 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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

[BIRC8_HUMAN] Protects against apoptosis mediated by BAX. [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]

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

Several IAP (inhibitor of apoptosis) proteins regulate cell fate decisions, and the X-linked IAP (XIAP) does so in part by inhibiting caspases, proteases that execute the apoptotic pathway. A tissue-specific homologue of XIAP, known as ILP2 (IAP-like protein 2), has previously been implicated in the control of apoptosis in the testis by direct inhibition of caspase 9. In examining this protein we found that the putative caspase 9 interaction domain is a surprisingly weak inhibitor and is also conformationally unstable. Comparison with the equivalent domain in XIAP demonstrated that the instability is due to the lack of a linker segment N-terminal to the inhibitory BIR (baculovirus IAP repeat) domain. Fusion of a 9-residue linker from XIAP to the N-terminus of ILP2 restored tight caspase 9 inhibition, dramatically increased conformational stability and allowed crystallization of the ILP2 BIR domain in a form strikingly similar to the XIAP third BIR domain. We conclude that ILP2 is an unstable protein, and cannot inhibit caspase 9 in a physiological way on its own. We speculate that ILP2 requires assistance from unidentified cellular factors to be an effective inhibitor of apoptosis in vivo.

The BIR domain of IAP-like protein 2 is conformationally unstable: implications for caspase inhibition.,Shin H, Renatus M, Eckelman BP, Nunes VA, Sampaio CA, Salvesen GS Biochem J. 2005 Jan 1;385(Pt 1):1-10. PMID:15485395^[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
↑ Shin H, Renatus M, Eckelman BP, Nunes VA, Sampaio CA, Salvesen GS. The BIR domain of IAP-like protein 2 is conformationally unstable: implications for caspase inhibition. Biochem J. 2005 Jan 1;385(Pt 1):1-10. PMID:15485395 doi:10.1042/BJ20041107

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 See Also
7 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1xb1"

@@ Line 1: / Line 1: @@
 ==The Structure of the BIR domain of IAP-like protein 2==
 <StructureSection load='1xb1' size='340' side='right' caption='[[1xb1]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
@@ Line 6: / Line 7: @@
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1xb0|1xb0]]</td></tr>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BIRC8, ILP2 ([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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1xb1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1xb1 OCA], [http://pdbe.org/1xb1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1xb1 RCSB], [http://www.ebi.ac.uk/pdbsum/1xb1 PDBsum]</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=1xb1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1xb1 OCA], [http://pdbe.org/1xb1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1xb1 RCSB], [http://www.ebi.ac.uk/pdbsum/1xb1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1xb1 ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 16: / Line 17: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/xb/1xb1_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/xb/1xb1_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>

1xb1

From Proteopedia

Revision as of 06:57, 18 April 2018

The Structure of the BIR domain of IAP-like protein 2

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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