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Importin-beta is a GDP-to-GTP exchange factor of Ran: implications for the mechanism of nuclear import.

Ran-GTP interacts strongly with importin-beta, and this interaction promotes the release of the importin-alpha-nuclear localization signal cargo from importin-beta. Ran-GDP also interacts with importin-beta, but this interaction is 4 orders of magnitude weaker than the Ran-GTP.importin-beta interaction. Here we use the yeast complement of nuclear import proteins to show that the interaction between Ran-GDP and importin-beta promotes the dissociation of GDP from Ran. The release of GDP from the Ran-GDP-importin-beta complex stabilizes the complex, which cannot be dissociated by importin-alpha. Although Ran has a higher affinity for GDP compared with GTP, Ran in complex with importin-beta has a higher affinity for GTP. This feature is responsible for the generation of Ran-GTP from Ran-GDP by importin-beta. Ran-binding protein-1 (RanBP1) activates this reaction by forming a trimeric complex with Ran-GDP and importin-beta. Importin-alpha inhibits the GDP exchange reaction by sequestering importin-beta, whereas RanBP1 restores the GDP nucleotide exchange by importin-beta by forming a tetrameric complex with importin-beta, Ran, and importin-alpha. 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.

Pubmed ID: 19549784

Authors

  • Lonhienne TG
  • Forwood JK
  • Marfori M
  • Robin G
  • Kobe B
  • Carroll BJ

Journal

The Journal of biological chemistry

Publication Data

August 21, 2009

Associated Grants

None

Mesh Terms

  • Active Transport, Cell Nucleus
  • Chromatography, Gel
  • Chromatography, High Pressure Liquid
  • Guanine Nucleotide Exchange Factors
  • Guanosine Diphosphate
  • Guanosine Triphosphate
  • Humans
  • Nuclear Proteins
  • Protein Binding
  • alpha Karyopherins
  • beta Karyopherins
  • ran GTP-Binding Protein