Abstract
Ran-GTP interacts strongly with importin-ß, and this interaction promotes the release of the importin-'-nuclear localization signal cargo from importin-ß. Ran-GDP also interacts with importin-ß, but this interaction is 4 orders of magnitude weaker than the Ran-GTP·importin-ß interaction. Here we use the yeast complement of nuclear import proteins to show that the interaction between Ran-GDP and importin-ß promotes the dissociation of GDP from Ran. The release of GDP from the Ran-GDP-importin-ß complex stabilizes the complex, which cannot be dissociated by importin-'. Although Ran has a higher affinity for GDP compared with GTP, Ran in complex with importin-ß has a higher affinity for GTP. This feature is responsible for the generation of Ran-GTP from Ran-GDP by importin-ß. Ran-binding protein-1 (RanBP1) activates this reaction by forming a trimeric complex with Ran-GDP and importin-ß. Importin-' inhibits the GDP exchange reaction by sequestering importin-ß, whereas RanBP1 restores the GDP nucleotide exchange by importin-ß by forming a tetrameric complex with importin-ß, Ran, and importin-'. The exchange is also inhibited by nuclear-transport factor-2 (NTF2). We suggest a mechanism for nuclear import, additional to the established RCC1 (Ran-guanine exchange factor)-dependent pathway that incorporates these results.
Original language | English |
---|---|
Pages (from-to) | 22549-22558 |
Number of pages | 10 |
Journal | Journal of Biological Chemistry |
Volume | 284 |
Issue number | 34 |
DOIs | |
Publication status | Published - 2009 |