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
Jade K ForwoodB Kobe

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.

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Citations

Jun 25, 2009·The Journal of Biological Chemistry·Thierry G LonhienneBernard J Carroll
May 30, 2009·Acta Crystallographica. Section F, Structural Biology and Crystallization Communications·Noelia RomanJade K Forwood
Nov 3, 2015·Journal of Molecular Biology·Mary ChristieBostjan Kobe
Jun 11, 2009·IUBMB Life·Laura M McLane, Anita H Corbett
Oct 28, 2010·Biochimica Et Biophysica Acta·Mary MarforiBostjan Kobe
Oct 30, 2010·Biochimica Et Biophysica Acta·Yuh Min Chook, Katherine E Süel
Sep 3, 2017·The Journal of Cell Biology·Larisa E KapinosRoderick Y H Lim
Jan 15, 2020·Journal of Cell Science·Suncica BarbatoRoderick Y H Lim
Jul 24, 2013·The Journal of Biological Chemistry·Oliver TaltynovZeger Debyser
Jun 16, 2016·Acta Crystallographica. Section D, Structural Biology·Marcel J TauchertAchim Dickmanns
Nov 4, 2017·Protein Science : a Publication of the Protein Society·Mary Ashley RimmerGerald M Carlson
Aug 8, 2015·The Journal of Biological Chemistry·Volkan SakinFrauke Melchior
Apr 30, 2021·Journal of Cell Science·Joanna KalitaRoderick Y H Lim

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