title: Conformational variability of nucleo-cytoplasmic transport factors.
abstract: The transport of macromolecules between the nucleus and cytoplasm of eukaryotic cells is largely mediated by a single family of transport factors, the karyopherin or importin beta-like family. Structural and biochemical evidence suggests conformational flexibility of these modular HEAT-repeat proteins is crucial for their regulation. Here we use small angle x-ray scattering to assess the extent of conformational variation within a set of nuclear import and export factors. The study reveals that importin beta, transportin, and the exportin Xpo-t share a similar S-like superhelical conformation in their unbound state. There are no obvious differences in the overall structures that might generally distinguish nuclear export from nuclear import mediators. Two other members of the family, the exportins Cse1 and Xpo1, possess a significantly more globular conformation, indicating that the extended S-like architecture is not a hallmark of all karyopherins. Binding of RanGTP/cargo to importin beta, transportin, and Xpo-t triggers distinct conformational responses, suggesting that even closely related karyopherins employ different mechanisms of conformational regulation and that cargo and nuclear pore-interacting surfaces of the different receptors may be unique.
authors.affiliation: European Molecular Biology Laboratory, Meyerhofstrasse 1, D-69117 Heidelberg, Germany.
authors.forename: Noemi
authors.initials: N
authors.lastname: Fukuhara
authors.forename: Elena
authors.initials: E
authors.lastname: Fernandez
authors.forename: Judith
authors.initials: J
authors.lastname: Ebert
authors.forename: Elena
authors.initials: E
authors.lastname: Conti
authors.forename: Dmitri
authors.initials: D
authors.lastname: Svergun
mesh_terms: D028884:Karyopherins / Q000737:chemistry* / Q000502:physiology; D011487:Protein Conformation; D012542:Scattering, Radiation; D014965:X-Rays; D020931:ran GTP-Binding Protein / Q000737:chemistry
chemical_list: D028884:Karyopherins; D020931:ran GTP-Binding Protein