Importin-B is a GDP-to-GTP exchange factor of Ran: Implications for the mechanism of nuclear import

Lonhienne, Thierry G., Forwood, Jade K., Marfori, Mary, Robin, Gautier, Kobe, Bostjan and Carroll, Bernard J. (2009) Importin-B is a GDP-to-GTP exchange factor of Ran: Implications for the mechanism of nuclear import. Journal of Biological Chemistry, 284 34: 22549-22558. doi:10.1074/jbc.M109.019935

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Author Lonhienne, Thierry G.
Forwood, Jade K.
Marfori, Mary
Robin, Gautier
Kobe, Bostjan
Carroll, Bernard J.
Title Importin-B is a GDP-to-GTP exchange factor of Ran: Implications for the mechanism of nuclear import
Formatted title
Importin-β is a GDP-to-GTP exchange factor of Ran: Implications for the mechanism of nuclear import
Journal name Journal of Biological Chemistry   Check publisher's open access policy
ISSN 0021-9258
Publication date 2009-08-21
Year available 2009
Sub-type Article (original research)
DOI 10.1074/jbc.M109.019935
Open Access Status File (Publisher version)
Volume 284
Issue 34
Start page 22549
End page 22558
Total pages 10
Editor Herbert Tabor
Place of publication Pike, Bethesda, U.S.A.
Publisher American Society for Biochemistry and Molecular Biology Inc
Language eng
Subject C1
060108 Protein Trafficking
970106 Expanding Knowledge in the Biological Sciences
Abstract 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 theGDPexchange 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.
Keyword Protein Import
Nucleocytoplasmic transport
Binding protein
Pore complex
RCC1
Alpha
P97
NTF2
Nucleoporins
Association
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

 
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Created: Thu, 03 Sep 2009, 17:42:16 EST by Mr Andrew Martlew on behalf of Centre for Integrative Legume Research