title: The l2 minor capsid protein of human papillomavirus type 16 interacts with a network of nuclear import receptors.
abstract: The L2 minor capsid proteins enter the nucleus twice during viral infection: in the initial phase after virion disassembly and in the productive phase when, together with the L1 major capsid proteins, they assemble the replicated viral DNA into virions. In this study we investigated the interactions between the L2 protein of high-risk human papillomavirus type 16 (HPV16) and nuclear import receptors. We discovered that HPV16 L2 interacts directly with both Kapbeta(2) and Kapbeta(3). Moreover, binding of Ran-GTP to either Kapbeta(2) or Kapbeta(3) inhibits its interaction with L2, suggesting that the Kapbeta/L2 complex is import competent. In addition, we found that L2 forms a complex with the Kapalpha(2)beta(1) heterodimer via interaction with the Kapalpha(2) adapter. In agreement with the binding data, nuclear import of L2 in digitonin-permeabilized cells could be mediated by either Kapalpha(2)beta(1) heterodimers, Kapbeta(2), or Kapbeta(3). Mapping studies revealed that HPV16 L2 contains two nuclear localization signals (NLSs), in the N terminus (nNLS) and C terminus (cNLS), that could mediate its nuclear import. Together the data suggest that HPV16 L2 interacts via its NLSs with a network of karyopherins and can enter the nucleus via several import pathways mediated by Kapalpha(2)beta(1) heterodimers, Kapbeta(2), and Kapbeta(3).
authors.affiliation: Biology Department, Boston College, Higgins Hall Room 578, 140 Commonwealth Avenue, Chestnut Hill, MA 02467, USA.
authors.forename: Medha S
authors.initials: MS
authors.lastname: Darshan
authors.forename: John
authors.initials: J
authors.lastname: Lucchi
authors.forename: Emily
authors.initials: E
authors.lastname: Harding
authors.forename: Junona
authors.initials: J
authors.lastname: Moroianu
mesh_terms: D021581:Active Transport, Cell Nucleus; D000595:Amino Acid Sequence; D036022:Capsid Proteins / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D019913:Nuclear Localization Signals; D009856:Oncogene Proteins, Viral / Q000378:metabolism*; D028961:beta Karyopherins / Q000378:metabolism*
chemical_list: D036022:Capsid Proteins; C063316:L2 protein, Human papillomavirus type 16; D019913:Nuclear Localization Signals; D009856:Oncogene Proteins, Viral; C108121:TNPO1 protein, human; D028961:beta Karyopherins