Wolff T, Unterstab G, Heins G, Richt J A, Kann M (2002): Characterization of an unusual importin alpha binding motif in the Borna disease virus p10 protein which directs nuclear import
J. Biol. Chem. 277 (14): 12151-12157, published online 16. Januar 2002, 10.1074/jbc.M109103200.

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.

Further Information: www.jbc.org/cgi/content/abstract/M109103200v1