Reference: Lonhienne TG, et al. (2009) Importin-{beta} Is a GDP-to-GTP Exchange Factor of Ran: IMPLICATIONS FOR THE MECHANISM OF NUCLEAR IMPORT. J Biol Chem 284(34):22549-58

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Abstract

Ran-GTP interacts strongly with importin-beta and this interaction promotes the release of the importin-alpha:NLS cargo from importin-beta. Ran-GDP also interacts with importin-beta, but this interaction is four 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 stabilises the complex, which cannot be dissociated by importin-alpha. While Ran has a higher affinity for GDP compared to 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, while 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 (RanGEF)-dependent pathway that incorporates these results.

Reference Type
Journal Article
Authors
Lonhienne TG, Forwood JK, Marfori M, Robin G, Kobe B, Carroll BJ
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