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1g73

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(New page: 200px<br /> <applet load="1g73" size="450" color="white" frame="true" align="right" spinBox="true" caption="1g73, resolution 2.0&Aring;" /> '''CRYSTAL STRUCTURE OF...)
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Revision as of 14:54, 12 November 2007

Image:1g73.gif

1g73, resolution 2.0Å

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CRYSTAL STRUCTURE OF SMAC BOUND TO XIAP-BIR3 DOMAIN

Contents

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.

Disease

Known diseases associated with this structure: Lymphoproliferative syndrome, X-linked, 2 OMIM:[300079]

About this Structure

1G73 is a Protein complex structure of sequences from Homo sapiens with ZN as ligand. 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

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