1g73

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[[Image:1g73.gif|left|200px]]
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{{Structure
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|GENE= SMAC ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
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{{STRUCTURE_1g73| PDB=1g73 | SCENE= }}
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|RELATEDENTRY=[[1few|1FEW]]
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1g73 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1g73 OCA], [http://www.ebi.ac.uk/pdbsum/1g73 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1g73 RCSB]</span>
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'''CRYSTAL STRUCTURE OF SMAC BOUND TO XIAP-BIR3 DOMAIN'''
'''CRYSTAL STRUCTURE OF SMAC BOUND TO XIAP-BIR3 DOMAIN'''
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[[Category: Wu, G.]]
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[[Category: Wu, J W.]]
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[[Category: Helix bundle]]
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[[Category: zinc-binding domain]]
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[[Category: Zinc-binding domain]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 17:13:21 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 20:37:59 2008''
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Revision as of 14:13, 2 May 2008

Image:1g73.gif

Template:STRUCTURE 1g73

CRYSTAL STRUCTURE OF SMAC BOUND TO XIAP-BIR3 DOMAIN


Overview

Apoptosis is an essential process in the development and homeostasis of all metazoans. The inhibitor-of-apoptosis (IAP) proteins suppress cell death by inhibiting the activity of caspases; this inhibition is performed by the zinc-binding BIR domains of the IAP proteins. The mitochondrial protein Smac/DIABLO promotes apoptosis by eliminating the inhibitory effect of IAPs through physical interactions. Amino-terminal sequences in Smac/DIABLO are required for this function, as mutation of the very first amino acid leads to loss of interaction with IAPs and concomitant loss of Smac/DIABLO function. Here we report the high-resolution crystal structure of Smac/DIABLO complexed with the third BIR domain (BIR3) of XIAP. Our results show that the N-terminal four residues (Ala-Val-Pro-Ile) in Smac/DIABLO recognize a surface groove on BIR3, with the first residue Ala binding a hydrophobic pocket and making five hydrogen bonds to neighbouring residues on BIR3. These observations provide a structural explanation for the roles of the Smac N terminus as well as the conserved N-terminal sequences in the Drosophila proteins Hid/Grim/Reaper. In conjunction with other observations, our results reveal how Smac may relieve IAP inhibition of caspase-9 activity. In addition to explaining a number of biological observations, our structural analysis identifies potential targets for drug screening.

About this Structure

1G73 is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Structural basis of IAP recognition by Smac/DIABLO., Wu G, Chai J, Suber TL, Wu JW, Du C, Wang X, Shi Y, Nature. 2000 Dec 21-28;408(6815):1008-12. PMID:11140638 Page seeded by OCA on Fri May 2 17:13:21 2008

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