2RAW

Crystal structure of the Borealin-Survivin complex

2RAW の概要

• エントリーDOI: 10.2210/pdb2raw/pdb
• 関連するPDBエントリー: 2RAX
• 分子名称: Baculoviral IAP repeat-containing protein 5, Borealin, ZINC ION (3 entities in total)
• 機能のキーワード: cell cycle, dasrab, chromosomal passender complex, iap, bir, apoptosis, cell division, centromere, chromosomal protein, metal-binding, mitosis, nucleus, phosphorylation, protease inhibitor, thiol protease inhibitor
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Cytoplasm: O15392; Nucleus, nucleolus: Q53HL2
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 25027.94

構造登録者

Hymowitz, S.G. (登録日: 2007-09-17, 公開日: 2007-10-30, 最終更新日: 2023-08-30)

主引用文献

Bourhis, E.,Hymowitz, S.G.,Cochran, A.G.
The mitotic regulator Survivin binds as a monomer to its functional interactor Borealin.
J.Biol.Chem., 282:35018-35023, 2007

PubMed Abstract: 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.

PubMed: 17881355
DOI: 10.1074/jbc.M706233200

実験手法

X-RAY DIFFRACTION (2.4 Å)