Nuclear import strategies of high-risk HPV18 L2 minor capsid protein

Nuclear import strategies of high-risk HPV18 L2 minor capsid protein
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DOI:
10.1016/j.virol.2006.04.007
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发表时间:
2006-08-15
期刊:
影响因子:
3.7
通讯作者:
Moroianu, J.
Moroianu, J.
中科院分区:
医学3区
文献类型:
--
作者:
Klucevsek, K.;Daley, J.;Moroianu, J.

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我们研究了高危型HPV 18 L2次要衣壳蛋白的核输入策略。HPV 18 L2与KaP U2接头以及Kap β(2)和Kap β(3)核输入受体相互作用。此外,RanGTP与Kap 2或Kap 03的结合抑制它们与L2的相互作用,表明这些Kap β/L2复合物是输入感受态的。定位研究表明HPV 18 L2含有两个NLS:在N端(nNLS)和在C端(cNLS),它们都可以独立地介导核输入。nNLS和cNLS都与Kap α(2)β(1)异源二聚体形成复合物,并通过经典途径介导核输入。nNLS对于HPV 18 L2与Kap beta(2)和Kap M的相互作用也至关重要。有趣的是,nNLS和cNLS都与病毒DNA相互作用,并且这种DNA结合在没有核苷酸序列特异性的情况下发生。总之,这些数据表明HPV 18 L2可以通过其NLS与几种Kap和病毒DNA相互作用,并且可以通过由Kap α(2)β(1)异二聚体、Kap β(2)和Kap β(3)介导的多种输入途径进入细胞核。(c)2006爱思唯尔公司All rights reserved.
We have investigated the nuclear import strategies of high-risk HPV18 L2 minor capsid protein. HPV18 L2 interacts with KaP U2 adapter, and Kap beta(2) and Kap beta(3) nuclear import receptors. Moreover, binding of RanGTP to either Kap 2 or Kap 03 inhibits their interaction with L2, suggesting that these Kap beta/L2 complexes are import competent. Mapping studies show that HPV18 L2 contains two NLSs: in the N-terminus (nNLS) and in the C-terminus (cNLS), both of which can independently mediate nuclear import, Both nNLS and cNLS form a complex with Kap alpha(2)beta(1) heterodimer and mediate nuclear import via a classical pathway. The nNLS is also essential for the interaction of HPV18 L2 with Kap beta(2) and Kap M. Interestingly, both nNLS and cNLS interact with the viral DNA and this DNA binding occurs without nucleotide sequence specificity. Together, the data suggest that HPV18 L2 can interact via its NLSs with several Kaps and the viral DNA and may enter the nucleus via multiple import pathways mediated by Kap alpha(2)beta(1) heterodimers, Kap beta(2) and Kap beta(3). (c) 2006 Elsevier Inc. All rights reserved.