The adoption of a twisted structure of importin-β is essential for the protein-protein interaction required for nuclear transport

Importin-beta is a nuclear transport factor which mediates the nuclear import of various nuclear proteins. The N-terminal 1-449 residue fragment of mouse importin-beta (imp beta 449) possesses the ability to bidirectionally translocate through the nuclear pore complex (NPC), and to bind RanGTP. The structure of the uncomplexed form of imp beta 449 has been solved at a 2.6 Angstrom resolution by X-ray crystallography. It consists of ten copies of the tandemly arrayed HEAT repeat and exhibits conformational flexibility which is involved in protein-protein interaction for nuclear transport. The overall conformation of the HEAT repeats shows that a twisted motion produces a significantly varied superhelical architecture from the previously reported structure of RanGTP-bound importin-beta. These conformational changes appear to be the sum of small conformational changes throughout the polypeptide. Such a flexibility, which resides in the stacked HEAT repeats, is essential for interaction with RanGTP or with NPCs. Furthermore, it was found that imp beta 449 has a structural similarity with another nuclear migrating protein, namely beta-catenin, which is composed of another type of helix-repeated structure of ARM repeat, interestingly, the essential regions for NPC translocation for both importin-beta and beta-catenin are spatially well. overlapped with one another. This strongly indicates the importance of helix stacking of the HEAT or ARM repeats for NPC-passage. (C) 2000 Academic Press.