Structure of the nuclear transport complex karyopherin-beta2-Ran x GppNHp.

Transport factors in the karyopherin-beta (also called importin-beta) family mediate the movement of macromolecules in nuclear-cytoplasmic transport pathways. Karyopherin-beta2 (transportin) binds a cognate import substrate and targets it to the nuclear pore complex. In the nucleus, Ran x GTP binds karyopherin-beta2 and dissociates the substrate. Here we present the 3.0 ...
A structure of the karyopherin-beta2-Ran x GppNHp complex where GppNHp is a non-hydrolysable GTP analogue. Karyopherin-beta2 contains eighteen HEAT repeats arranged into two continuous orthogonal arches. Ran is clamped in the amino-terminal arch and substrate-binding activity is mapped to the carboxy-terminal arch. A large loop in HEAT repeat 7 spans both arches. Interactions of the loop with Ran and the C-terminal arch implicate it in GTPase-mediated dissociation of the import-substrate. Ran x GppNHp in the complex shows extensive structural rearrangement, compared to Ran GDP, in regions contacting karyopherin-beta2. This provides a structural basis for the specificity of the karyopherin-beta family for the GTP-bound state of Ran, as well as a rationale for interactions of the karyopherin-Ran complex with the regulatory proteins ranGAP, ranGEF and ranBP1.
Mesh Terms:
Amino Acid Sequence, Biological Transport, Cell Nucleus, Crystallography, X-Ray, Escherichia coli, Guanosine Triphosphate, Guanylyl Imidodiphosphate, Humans, Karyopherins, Macromolecular Substances, Models, Molecular, Molecular Sequence Data, Nuclear Proteins, Protein Conformation, Receptors, Cytoplasmic and Nuclear, Recombinant Proteins, Repetitive Sequences, Amino Acid, ran GTP-Binding Protein
Nature
Date: May. 20, 1999
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