Importin α nuclear localization signal binding sites for STAT1, STAT2, and influenza a virus nucleoprotein
Importin α nuclear localization signal binding sites for STAT1, STAT2, and influenza a virus nucleoprotein
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DOI：
10.1074/jbc.m303571200
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发表时间：
2003-07-25
影响因子：
4.8
通讯作者：
Julkunen, I
中科院分区：
文献类型：
--
作者：
Melén, K;Fagerlund, R;Julkunen, I
通过经典的核输入途径进入细胞核的蛋白质含有核定位信号（NLSs），这些信号被输入α分子家族识别。Importin α含有10个犰狳（臂）重复序列，其中n端臂重复2-4被认为是NLS的“主要”结合位点。干扰素激活的二聚体信号转导和转录激活因子（STAT1和STAT2）通过二聚体非经典NLS直接与输入蛋白α 5结合。在这里，我们通过位点定向突变表明，输入蛋白α 5的c端臂重复8和9形成STAT1同型二聚体和STAT1- stat2异源二聚体的独特结合位点。甲型流感病毒核蛋白还含有非经典NLS，可被输入蛋白α 5的c端NLS结合位点识别，包括臂重复序列7-9。甲型流感病毒核蛋白与输入蛋白α 3的结合也通过c末端臂重复序列发生。猿猴病毒40大T抗原与输入蛋白α 3的主要N端臂重复序列结合，表明一个输入蛋白α分子能够使用其N端或c端臂重复序列结合各种含有NLS的蛋白质。
Proteins actively transported into the nucleus via the classical nuclear import pathway contain nuclear localization signals (NLSs), which are recognized by the family of importin alpha molecules. Importin alpha contains 10 armadillo (arm) repeats, of which the N-terminal arm repeats 2-4 have been considered as the "major" NLS binding site. Interferon-activated, dimerized signal transducers and activators of transcription (STAT1 and STAT2) directly bind to importin alpha5 via a dimeric non-classical NLS. Here we show by site-directed mutagenesis that the very C-terminal arm repeats 8 and 9 of importin alpha5 form a unique binding site for STAT1 homodimers and STAT1-STAT2 heterodimers. Influenza A virus nucleoprotein also contains a nonclassical NLS that is recognized by the C-terminal NLS binding site of importin alpha5, comprising arm repeats 7-9. Binding of influenza A virus nucleoprotein to importin alpha3 also occurs via the C-terminal arm repeats. Simian virus 40 large T antigen instead binds to the major N-terminal arm repeats of importin alpha3, indicating that one importin alpha molecule is able to use either its N- or C-terminal arm repeats for binding various NLS containing proteins.