3EA5

Kap95p Binding Induces the Switch Loops of RanGDP to adopt the GTP-bound Conformation: Implications for Nuclear Import Complex Assembly Dynamics

Summary for 3EA5

• Entry DOI: 10.2210/pdb3ea5/pdb
• Descriptor: GTP-binding nuclear protein Ran, Importin subunit beta-1, GUANOSINE-5'-DIPHOSPHATE, ... (5 entities in total)
• Functional Keywords: karyopherin, importin, ran, gtp-binding, host-virus interaction, nucleotide-binding, nucleus, phosphoprotein, protein transport, transport, transport protein
• Biological source: Homo sapiens (human); More
• Cellular location: Nucleus: P62826; Cytoplasm (By similarity): Q06142
• Total number of polymer chains: 4
• Total formula weight: 239678.54

Authors

Forwood, J.K.,Lonhienne, J.K.,Guncar, G.,Stewart, M.,Marfori, M.,Kobe, B. (deposition date: 2008-08-24, release date: 2008-10-21, Last modification date: 2024-02-21)

Primary citation

Forwood, J.K.,Lonhienne, T.G.,Marfori, M.,Robin, G.,Meng, W.,Guncar, G.,Liu, S.M.,Stewart, M.,Carroll, B.J.,Kobe, B.
Kap95p binding induces the switch loops of RanGDP to adopt the GTP-bound conformation: implications for nuclear import complex assembly dynamics.
J.Mol.Biol., 383:772-782, 2008

PubMed 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.

PubMed: 18708071
DOI: 10.1016/j.jmb.2008.07.090

Experimental method

X-RAY DIFFRACTION (2.5 Å)