1g73
From Proteopedia
(New page: 200px<br /> <applet load="1g73" size="450" color="white" frame="true" align="right" spinBox="true" caption="1g73, resolution 2.0Å" /> '''CRYSTAL STRUCTURE OF...) |
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| - | [[Image:1g73.gif|left|200px]]<br /> | + | [[Image:1g73.gif|left|200px]]<br /><applet load="1g73" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1g73" size=" | + | |
caption="1g73, resolution 2.0Å" /> | caption="1g73, resolution 2.0Å" /> | ||
'''CRYSTAL STRUCTURE OF SMAC BOUND TO XIAP-BIR3 DOMAIN'''<br /> | '''CRYSTAL STRUCTURE OF SMAC BOUND TO XIAP-BIR3 DOMAIN'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Apoptosis is an essential process in the development and homeostasis of | + | 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== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1G73 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with ZN as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 1G73 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=ZN:'>ZN</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1G73 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Chai, J.]] | [[Category: Chai, J.]] | ||
[[Category: Shi, Y.]] | [[Category: Shi, Y.]] | ||
| - | [[Category: Suber, T | + | [[Category: Suber, T L.]] |
[[Category: Wu, G.]] | [[Category: Wu, G.]] | ||
| - | [[Category: Wu, J | + | [[Category: Wu, J W.]] |
[[Category: ZN]] | [[Category: ZN]] | ||
[[Category: helix bundle]] | [[Category: helix bundle]] | ||
[[Category: zinc-binding domain]] | [[Category: zinc-binding domain]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:46:50 2008'' |
Revision as of 10:46, 21 February 2008
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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 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
Page seeded by OCA on Thu Feb 21 12:46:50 2008
Categories: Homo sapiens | Protein complex | Chai, J. | Shi, Y. | Suber, T L. | Wu, G. | Wu, J W. | ZN | Helix bundle | Zinc-binding domain
