3KND

TPX2:importin-alpha complex

3KND の概要

• エントリーDOI: 10.2210/pdb3knd/pdb
• 分子名称: Importin subunit alpha-2, Targeting protein for Xklp2, SULFATE ION, ... (4 entities in total)
• 機能のキーワード: mitosis, importin, transport, protein transport
• 由来する生物種: Mus musculus (mouse); 詳細
• 細胞内の位置: Cytoplasm : P52293
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 59683.77

構造登録者

Stewart, M. (登録日: 2009-11-12, 公開日: 2010-03-23, 最終更新日: 2023-09-06)

主引用文献

Giesecke, A.,Stewart, M.
Novel binding of the mitotic regulator TPX2 (target protein for Xenopus kinesin-like protein 2) to importin-alpha.
J.Biol.Chem., 285:17628-17635, 2010

PubMed Abstract: Several aspects of mitotic spindle assembly are orchestrated by the Ran GTPase through its modulation of the interaction between spindle assembly factors and importin-alpha. One such factor is TPX2 that promotes microtubule assembly in the vicinity of chromosomes. TPX2 is inhibited when bound to importin-alpha, which occurs when the latter is bound to importin-beta. The importin-alpha:beta interaction is disrupted by the high RanGTP concentration near the chromosomes, releasing TPX2. In more distal regions, where Ran is predominantly GDP-bound, TPX2 remains bound to importin-alpha and so is inhibited. Here we use a combination of structural and biochemical methods to define the basis for TPX2 binding to importin-alpha. A 2.2 A resolution crystal structure shows that the primary nuclear localization signal ((284)KRKH(287)) of TPX2, which has been shown to be crucial for inhibition, binds to the minor NLS-binding site on importin-alpha. This atypical interaction pattern was confirmed using complementary binding studies that employed importin-alpha variants in which binding to either the major or minor NLS-binding site was impaired, together with competition assays using the SV40 monopartite NLS that binds primarily to the major site. The different way in which TPX2 binds to importin-alpha could account for much of the selectivity necessary during mitosis because this would reduce the competition for binding to importin-alpha from other NLS-containing proteins.

PubMed: 20335181
DOI: 10.1074/jbc.M110.102343

実験手法

X-RAY DIFFRACTION (2.151 Å)