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

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.