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  • Characterization of an unusual importin alpha binding motif in the borna disease virus p10 protein that directs nuclear import #MMPMID11796712
  • Wolff T; Unterstab G; Heins G; Richt JA; Kann M
  • J Biol Chem 2002[Apr]; 277 (14): 12151-7 PMID11796712garesp_yesshow ga
  • 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.
  • |Active Transport, Cell Nucleus[MESH]
  • |Amino Acid Motifs[MESH]
  • |Amino Acid Sequence[MESH]
  • |Cell Line[MESH]
  • |Cell Nucleus/*metabolism[MESH]
  • |DNA Mutational Analysis[MESH]
  • |Glutathione Transferase/metabolism[MESH]
  • |Humans[MESH]
  • |Microscopy, Confocal[MESH]
  • |Molecular Sequence Data[MESH]
  • |Nuclear Localization Signals[MESH]
  • |Precipitin Tests[MESH]
  • |Protein Binding[MESH]
  • |Protein Isoforms[MESH]
  • |Protein Structure, Tertiary[MESH]
  • |Protein Transport[MESH]
  • |Viral Proteins/*metabolism[MESH]
  • |alpha Karyopherins/*chemistry/*metabolism[MESH]

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    12151 14.277 2002