2raw
From Proteopedia
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==Overview== | ==Overview== | ||
| - | Survivin is a member of the | + | Survivin is a member of the IAP (inhibitor of apoptosis) protein family, defined in part by the presence of a zinc-binding baculoviral inhibitory repeat (BIR) domain. Most BIR domains bind short sequences beginning with alanine, and in this manner, they recognize and block the action of key targets in apoptotic pathways. However, Survivin binds only very weakly to typical IAP ligands. Unique features of Survivin are the long C-terminal helix following the BIR domain and a short segment (linking the helix and BIR domains) that mediates Survivin homodimerization. Despite this detailed knowledge of the structure of Survivin itself, there is a current lack of understanding about how Survivin recognizes cellular binding partners, and consequently, many questions about Survivin function remain unanswered. We determined two co-crystal structures of Survivin and a minimal binding fragment from the chromosomal passenger protein Borealin, a well validated functional interactor. The interaction between Survivin and Borealin involves extensive packing between the long C-terminal helix of Survivin and a long Borealin helix. Surprisingly, an additional important interaction occurs between the Survivin homodimerization interface and a short segment of Borealin. This segment both structurally mimics and displaces one Survivin monomer. The relevance of this unexpected interaction was tested by mutagenesis of two key Borealin residues. Mutant Borealin introduced into HeLa cells failed to localize properly during mitosis and also caused mislocalization of other chromosomal passenger proteins. This suggests that the mutant is dominant-negative and confirms the functional importance of the interaction surface identified in the crystal structures. |
==About this Structure== | ==About this Structure== | ||
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==Reference== | ==Reference== | ||
| - | The mitotic regulator | + | The mitotic regulator Survivin binds as a monomer to its functional interactor Borealin., Bourhis E, Hymowitz SG, Cochran AG, J Biol Chem. 2007 Nov 30;282(48):35018-23. Epub 2007 Sep 19. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17881355 17881355] |
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
| - | [[Category: Hymowitz, S | + | [[Category: Hymowitz, S G.]] |
[[Category: ZN]] | [[Category: ZN]] | ||
[[Category: alternative splicing]] | [[Category: alternative splicing]] | ||
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[[Category: zinc]] | [[Category: zinc]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:46:00 2008'' |
Revision as of 16:46, 21 February 2008
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Crystal structure of the Borealin-Survivin complex
Overview
Survivin is a member of the IAP (inhibitor of apoptosis) protein family, defined in part by the presence of a zinc-binding baculoviral inhibitory repeat (BIR) domain. Most BIR domains bind short sequences beginning with alanine, and in this manner, they recognize and block the action of key targets in apoptotic pathways. However, Survivin binds only very weakly to typical IAP ligands. Unique features of Survivin are the long C-terminal helix following the BIR domain and a short segment (linking the helix and BIR domains) that mediates Survivin homodimerization. Despite this detailed knowledge of the structure of Survivin itself, there is a current lack of understanding about how Survivin recognizes cellular binding partners, and consequently, many questions about Survivin function remain unanswered. We determined two co-crystal structures of Survivin and a minimal binding fragment from the chromosomal passenger protein Borealin, a well validated functional interactor. The interaction between Survivin and Borealin involves extensive packing between the long C-terminal helix of Survivin and a long Borealin helix. Surprisingly, an additional important interaction occurs between the Survivin homodimerization interface and a short segment of Borealin. This segment both structurally mimics and displaces one Survivin monomer. The relevance of this unexpected interaction was tested by mutagenesis of two key Borealin residues. Mutant Borealin introduced into HeLa cells failed to localize properly during mitosis and also caused mislocalization of other chromosomal passenger proteins. This suggests that the mutant is dominant-negative and confirms the functional importance of the interaction surface identified in the crystal structures.
About this Structure
2RAW is a Protein complex structure of sequences from Homo sapiens with as ligand. Full crystallographic information is available from OCA.
Reference
The mitotic regulator Survivin binds as a monomer to its functional interactor Borealin., Bourhis E, Hymowitz SG, Cochran AG, J Biol Chem. 2007 Nov 30;282(48):35018-23. Epub 2007 Sep 19. PMID:17881355
Page seeded by OCA on Thu Feb 21 18:46:00 2008
Categories: Homo sapiens | Protein complex | Hymowitz, S G. | ZN | Alternative splicing | Apoptosis | Bir | Cell cycle | Cell division | Centromere | Chromosomal passender complex | Chromosomal protein | Cytoplasm | Dasrab | Iap | Metal-binding | Mitosis | Nucleus | Phosphorylation | Polymorphism | Protease inhibitor | Thiol protease inhibitor | Zinc
