1FEW

CRYSTAL STRUCTURE OF SMAC/DIABLO

Summary for 1FEW

• Entry DOI: 10.2210/pdb1few/pdb
• Descriptor: SECOND MITOCHONDRIA-DERIVED ACTIVATOR OF CASPASES (1 entity in total)
• Functional Keywords: smac, diablo, apoptosis, caspase activation, iap inhibition
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 20759.08

Authors

Chai, J.,Shi, Y. (deposition date: 2000-07-23, release date: 2000-09-13, Last modification date: 2024-02-07)

Primary citation

Chai, J.,Du, C.,Wu, J.W.,Kyin, S.,Wang, X.,Shi, Y.
Structural and biochemical basis of apoptotic activation by Smac/DIABLO.
Nature, 406:855-862, 2000

PubMed Abstract: 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.

PubMed: 10972280
DOI: 10.1038/35022514

Experimental method

X-RAY DIFFRACTION (2.2 Å)