Importin-Beta is a GDP-TO-GTP exchange factor of RAN: Implications for the mechanism of nuclear import.

Thierry G. Ionienne, Jade Forwood, Mary Marfori, Gautier Robin, Bostjan Kobe, Bernard J. Carroll

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)

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 languageEnglish
Pages (from-to)22549-22558
Number of pages10
JournalJournal of Biological Chemistry
Volume284
Issue number34
DOIs
Publication statusPublished - 2009

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