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| '''CRYSTAL STRUCTURE OF SMAC/DIABLO'''
| | ===CRYSTAL STRUCTURE OF SMAC/DIABLO=== |
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| ==Overview==
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| Apoptosis (programmed cell death), an essential process in the development and homeostasis of metazoans, is carried out by caspases. The mitochondrial protein Smac/DIABLO performs a critical function in apoptosis by eliminating the inhibitory effect of IAPs (inhibitor of apoptosis proteins) on caspases. Here we show that Smac/DIABLO promotes not only the proteolytic activation of procaspase-3 but also the enzymatic activity of mature caspase-3, both of which depend upon its ability to interact physically with IAPs. The crystal structure of Smac/DIABLO at 2.2 A resolution reveals that it homodimerizes through an extensive hydrophobic interface. Missense mutations inactivating this dimeric interface significantly compromise the function of Smac/DIABLO. As in the Drosophila proteins Reaper, Grim and Hid, the amino-terminal amino acids of Smac/DIABLO are indispensable for its function, and a seven-residue peptide derived from the amino terminus promotes procaspase-3 activation in vitro. These results establish an evolutionarily conserved structural and biochemical basis for the activation of apoptosis by Smac/DIABLO.
| | The line below this paragraph, {{ABSTRACT_PUBMED_10972280}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 10972280 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_10972280}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Iap inhibition]] | | [[Category: Iap inhibition]] |
| [[Category: Smac]] | | [[Category: Smac]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 16:14:35 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 1 03:08:36 2008'' |