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Kap95p binding induces the switch loops of RanGDP to adopt the GTP-bound conformation: implications for nuclear import complex assembly dynamics |
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| Authors: | Forwood Jade K Lonhienne Thierry G Marfori Mary Robin Gautier Meng Weining Guncar Gregor Liu Sai M Stewart Murray Carroll Bernard J Kobe Bostjan |
| Affiliation: | 1 School of Biomedical Sciences, Charles Sturt University, Wagga Wagga 2650, Australia 2 School of Molecular and Microbial Sciences, The University of Queensland, Brisbane, Queensland 4072, Australia 3 School of Crop, Land and Food Sciences, and ARC Centre of Excellence for Integrative Legume Research, The University of Queensland, Brisbane, Queensland 4072, Australia 4 Institute for Molecular Bioscience and Special Research Centre for Functional and Applied Genomics, The University of Queensland, Brisbane, Queensland 4072, Australia 5 Sir William Dunn School of Pathology, Oxford University, Oxford OX1 3RE, UK 6 MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK |
| 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. |
| Keywords: | GTP, guanosine 5&prime -triphosphate GDP, guanosine 5&prime -diphosphate GTPase, guanosine 5&prime -triphosphatase GAP, GTPase activating protein IBB, importin-β-binding NCS, non-crystallographic symmetry GST, glutathione-S-transferase TLS, translation-libration-screw |
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