Kap95p binding induces the switch loops of RanGDP to adopt the GTP-bound conformation: Implications for nuclear import complex assembly dynamics

Forwood, Jade K., Lonhienne, Thierry G., Marfori, Mary, Robin, Gautier, Meng, Weining, Guncar, Gregor, Liu, Sai M., Stewart, Murray, Carroll, Bernard J. and Kobe, Bostjan (2008) Kap95p binding induces the switch loops of RanGDP to adopt the GTP-bound conformation: Implications for nuclear import complex assembly dynamics. Journal of Molecular Biology, 383 4: 772-782. doi:10.1016/j.jmb.2008.07.090


Author Forwood, Jade K.
Lonhienne, Thierry G.
Marfori, Mary
Robin, Gautier
Meng, Weining
Guncar, Gregor
Liu, Sai M.
Stewart, Murray
Carroll, Bernard J.
Kobe, Bostjan
Title Kap95p binding induces the switch loops of RanGDP to adopt the GTP-bound conformation: Implications for nuclear import complex assembly dynamics
Journal name Journal of Molecular Biology   Check publisher's open access policy
ISSN 0022-2836
Publication date 2008-11-21
Year available 2008
Sub-type Article (original research)
DOI 10.1016/j.jmb.2008.07.090
Volume 383
Issue 4
Start page 772
End page 782
Total pages 11
Editor J. Karn
Place of publication Oxford
Publisher Elsevier
Language eng
Subject C1
060112 Structural Biology (incl. Macromolecular Modelling)
970106 Expanding Knowledge in the Biological Sciences
Abstract The asymmetric distribution of the nucleotide-bound state of Ran across the nuclear envelope is crucial for determining the directionality of nuclear transport. In the nucleus, Ran is primarily in the guanosine 5′-triphosphate (GTP)-bound state, whereas in the cytoplasm, Ran is primarily guanosine 5′-diphosphate (GDP)-bound. Conformational changes within the Ran switch I and switch II loops are thought to modulate its affinity for importin-β. Here, we show that RanGDP and importin-β form a stable complex with a micromolar dissociation constant. This complex can be dissociated by importin-β binding partners such as importin-α. Surprisingly, the crystal structure of the Kap95p–RanGDP complex shows that Kap95p induces the switch I and II regions of RanGDP to adopt a conformation that resembles that of the GTP-bound form. The structure of the complex provides insights into the structural basis for the gradation of affinities regulating nuclear protein transport.
Keyword nucleocytoplasmic transport
Ran
karyopherin
importin
protein structure
Q-Index Code C1
Q-Index Status Confirmed Code

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2009 Higher Education Research Data Collection
School of Chemistry and Molecular Biosciences
 
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Created: Thu, 26 Feb 2009, 01:25:05 EST by Jennifer Falknau on behalf of School of Chemistry & Molecular Biosciences