Klucevsek K, Daley J, Darshan M S, Bordeaux J, Moroianu J
Biology Department, Boston College, Higgins Hall, Room 578, 140 Commonwealth Avenue, Chestnut Hill, MA 02467, USA.
Virology. 2006 Aug 15;352(1):200-8. doi: 10.1016/j.virol.2006.04.007. Epub 2006 Jun 2.
We have investigated the nuclear import strategies of high-risk HPV18 L2 minor capsid protein. HPV18 L2 interacts with Kap alpha2 adapter, and Kap beta2 and Kap beta3 nuclear import receptors. Moreover, binding of RanGTP to either Kap beta2 or Kap beta3 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 alpha2beta1 heterodimer and mediate nuclear import via a classical pathway. The nNLS is also essential for the interaction of HPV18 L2 with Kap beta2 and Kap beta3. 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 alpha2beta1 heterodimers, Kap beta2 and Kap beta3.
我们研究了高危型人乳头瘤病毒18型（HPV18）次要衣壳蛋白L2的核输入策略。HPV18 L2与Kap alpha2衔接蛋白以及Kap beta2和Kap beta3核输入受体相互作用。此外，RanGTP与Kap beta2或Kap beta3的结合会抑制它们与L2的相互作用，这表明这些Kap beta/L2复合物具有核输入能力。定位研究表明，HPV18 L2含有两个核定位信号（NLS）：一个在N端（nNLS），另一个在C端（cNLS），二者均可独立介导核输入。nNLS和cNLS均与Kap alpha2beta1异二聚体形成复合物，并通过经典途径介导核输入。nNLS对于HPV18 L2与Kap beta2和Kap beta3的相互作用也至关重要。有趣的是，nNLS和cNLS均与病毒DNA相互作用，且这种DNA结合不具有核苷酸序列特异性。总之，这些数据表明，HPV18 L2可通过其NLS与多种Kap以及病毒DNA相互作用，并可能通过由Kap alpha2beta1异二聚体、Kap beta2和Kap beta3介导的多种输入途径进入细胞核。
