1G73

CRYSTAL STRUCTURE OF SMAC BOUND TO XIAP-BIR3 DOMAIN

Summary for 1G73

• Entry DOI: 10.2210/pdb1g73/pdb
• Related: 1FEW
• Descriptor: SECOND MITOCHONDRIA-DERIVED ACTIVATOR OF CASPASES, INHIBITORS OF APOPTOSIS-LIKE PROTEIN ILP, ZINC ION (3 entities in total)
• Functional Keywords: helix bundle, zinc-binding domain, apoptosis-apoptosis inhibitor complex, apoptosis/apoptosis inhibitor
• Biological source: Homo sapiens (human); More
• Cellular location: Mitochondrion: Q9NR28; Cytoplasm: P98170
• Total number of polymer chains: 4
• Total formula weight: 64212.36

Authors

Wu, G.,Chai, J.,Suber, T.L.,Wu, J.-W.,Shi, Y. (deposition date: 2000-11-08, release date: 2001-01-10, Last modification date: 2024-02-07)

Primary citation

Wu, G.,Chai, J.,Suber, T.L.,Wu, J.W.,Du, C.,Wang, X.,Shi, Y.
Structural basis of IAP recognition by Smac/DIABLO.
Nature, 408:1008-1012, 2000

PubMed Abstract: 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.

PubMed: 11140638
DOI: 10.1038/35050012

Experimental method

X-RAY DIFFRACTION (2 Å)