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

Abstract

We have investigated the nuclear import strategies of high-risk HPV18 L2 minor capsid protein. HPV18 L2 interacts with Kap α 2 adapter, and Kap β 2 and Kap β 3 nuclear import receptors. Moreover, binding of RanGTP to either Kap β 2 or Kap β 3 inhibits their interaction with L2, suggesting that these Kap β/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 α 2β 1 heterodimer and mediate nuclear import via a classical pathway. The nNLS is also essential for the interaction of HPV18 L2 with Kap β 2 and Kap β 3. 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 α 2β 1 heterodimers, Kap β 2 and Kap β 3.