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

Jade Forwood, Thierry Lonhienne, Mary Marfori, Robin Gautier, Weining Meng, Gregor Guncar, Sai M Liu, Murray Stewart, Bernard Carroll, Bostjan Kobe

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)
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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-beta. Here, we show that RanGDP and importin-beta form a stable complex with a micromolar dissociation constant. This complex can be dissociated by importin-beta binding partners such as importin-alpha. 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.
Original languageEnglish
Pages (from-to)772-782
Number of pages11
JournalJournal of Molecular Biology
Volume383
Issue number4
DOIs
Publication statusPublished - 2008

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