2raw
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Crystal structure of the Borealin-Survivin complex
OverviewOverview
Survivin is a member of the "inhibitor-of-apoptosis" protein family, defined in part by the presence of a zinc-binding 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 unanswered questions about Survivin function. 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 StructureAbout this Structure
2RAW is a Protein complex structure of sequences from Homo sapiens with ZN as ligand. Full crystallographic information is available from OCA.
ReferenceReference
The mitotic regulator survivin binds as a monomer to its functional interactor Borealin., Bourhis E, Hymowitz SG, Cochran AG, J Biol Chem. 2007 Sep 19;. PMID:17881355
Page seeded by OCA on Mon Nov 12 23:36:31 2007
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- 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