6IU7

Crystal structure of importin-alpha1 bound to the 53BP1 nuclear localization signal (wild-type)

6IU7 の概要

• エントリーDOI: 10.2210/pdb6iu7/pdb
• 関連するPDBエントリー: 6IUA
• 分子名称: Importin subunit alpha-1, Peptide from TP53-binding protein 1 (3 entities in total)
• 機能のキーワード: importin, nls, transport protein, transport protein-protein binding complex, transport protein/protein binding
• 由来する生物種: Mus musculus (Mouse); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 48751.83

構造登録者

Matsuura, Y. (登録日: 2018-11-27, 公開日: 2019-01-30, 最終更新日: 2023-11-22)

主引用文献

Matsuura, Y.
Structural and biochemical characterization of the recognition of the 53BP1 nuclear localization signal by importin-alpha.
Biochem. Biophys. Res. Commun., 510:236-241, 2019

PubMed Abstract: 53BP1 (TP53-binding protein 1) plays a key role in DNA double-strand break repair by promoting non-homologous end joining (NHEJ) especially during G1 phase of the cell cycle. Nuclear import of 53BP1 is required for proper localization of 53BP1 and maintenance of genome integrity. 53BP1 has a classical bipartite nuclear localization signal (NLS) of sequence 1666-GKRKLITSEEERSPAKRGRKS-1686. Ser1678 within the 53BP1 NLS can be phosphorylated by CDK1/cyclin B, and a phosphomimetic substitution of Ser1678 with aspartate has been shown to negatively regulate nuclear import of 53BP1. Here, the X-ray crystal structures of the nuclear import adaptor importin-α1 bound to the wild-type 53BP1 NLS and the S1678D mutant of 53BP1 NLS are reported at resolutions of 1.9 and 1.7 Å, respectively. In the wild-type structure, not only the two basic clusters of the 53BP1 NLS but also the linker region between the basic clusters made extensive interactions with importin-α1. In the mutant structure, the linker region between the basic clusters in the 53BP1 NLS made fewer interactions with importin-α1 than those observed in the wild-type structure. However, biochemical binding assays using purified proteins showed that the 53BP1 mutation S1678D reduces the binding affinity to importin-α1 only to a modest extent. Implications of these findings for regulatory mechanism of 53BP1 nuclear import are discussed.

PubMed: 30685087
DOI: 10.1016/j.bbrc.2019.01.075

実験手法

X-RAY DIFFRACTION (1.9 Å)