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| - | [[Image:1g73.gif|left|200px]] | + | {{Seed}} |
| | + | [[Image:1g73.png|left|200px]] |
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| | {{STRUCTURE_1g73| PDB=1g73 | SCENE= }} | | {{STRUCTURE_1g73| PDB=1g73 | SCENE= }} |
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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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| - | ==Overview==
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| - | 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.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_11140638}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 11140638 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_11140638}} |
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| | ==About this Structure== | | ==About this Structure== |
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| | [[Category: Helix bundle]] | | [[Category: Helix bundle]] |
| | [[Category: Zinc-binding domain]] | | [[Category: Zinc-binding domain]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 17:13:21 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 1 04:48:33 2008'' |
Revision as of 01:48, 1 July 2008
Template:STRUCTURE 1g73
CRYSTAL STRUCTURE OF SMAC BOUND TO XIAP-BIR3 DOMAIN
Template:ABSTRACT PUBMED 11140638
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 Tue Jul 1 04:48:33 2008
