title: Characterization of an unusual importin alpha binding motif in the borna disease virus p10 protein that directs nuclear import.
abstract: Nuclear import of many cellular and viral proteins is mediated by short nuclear localization signals (NLS) that are recognized by intracellular receptor proteins belonging to the importin/karyopherin alpha and beta families. The primary structure of NLS is not well defined, but most contain at least three basic amino acids and harbor the relative consensus sequence K(K/R)X(K/R). We have studied the nuclear import of the Borna disease virus p10 protein that lacks a canonical oligobasic NLS. It is shown that the p10 protein exhibits all characteristics of an actively transported molecule in digitonin-permeabilized cells. Import activity was found to reside in the 20 N-terminal p10 amino acids that are devoid of an NLS consensus motif. Unexpectedly, p10-dependent import was blocked by a peptide inhibitor of importin alpha-dependent nuclear translocation, and the transport activity of the p10 N-terminal domain was shown to correlate with the ability to bind to importin alpha. These findings suggest that nuclear import of the Borna disease virus p10 protein occurs through a nonconventional karyophilic signal and highlight that the cellular importin alpha NLS receptor proteins can recognize nuclear targeting signals that substantially deviate from the consensus sequence.
authors.affiliation: Robert-Koch-Institut, Nordufer 20, 13353 Berlin, Germany. wolfft@rki.de
authors.forename: Thorsten
authors.initials: T
authors.lastname: Wolff
authors.forename: Gunhild
authors.initials: G
authors.lastname: Unterstab
authors.forename: Gudrun
authors.initials: G
authors.lastname: Heins
authors.forename: Juergen A
authors.initials: JA
authors.lastname: Richt
authors.forename: Michael
authors.initials: M
authors.lastname: Kann
mesh_terms: D021581:Active Transport, Cell Nucleus; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D004252:DNA Mutational Analysis; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D018613:Microscopy, Confocal; D008969:Molecular Sequence Data; D019913:Nuclear Localization Signals; D011233:Precipitin Tests; D011485:Protein Binding; D020033:Protein Isoforms; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D014764:Viral Proteins / Q000378:metabolism*; D028901:alpha Karyopherins / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D019913:Nuclear Localization Signals; D020033:Protein Isoforms; D014764:Viral Proteins; D028901:alpha Karyopherins; C119397:p10 protein, Borna disease virus; D005982:Glutathione Transferase