title: The adoption of a twisted structure of importin-beta is essential for the protein-protein interaction required for nuclear transport.
abstract: 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 (impbeta449) possesses the ability to bidirectionally translocate through the nuclear pore complex (NPC), and to bind RanGTP. The structure of the uncomplexed form of impbeta449 has been solved at a 2.6 A 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 impbeta449 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.
authors.affiliation: Institute for Protein Research, Osaka University, 3-2 Yamada-oka, Osaka, Suita, 565-0871, Japan.
authors.forename: S J
authors.initials: SJ
authors.lastname: Lee
authors.forename: N
authors.initials: N
authors.lastname: Imamoto
authors.forename: H
authors.initials: H
authors.lastname: Sakai
authors.forename: A
authors.initials: A
authors.lastname: Nakagawa
authors.forename: S
authors.initials: S
authors.lastname: Kose
authors.forename: M
authors.initials: M
authors.lastname: Koike
authors.forename: M
authors.initials: M
authors.lastname: Yamamoto
authors.forename: T
authors.initials: T
authors.lastname: Kumasaka
authors.forename: Y
authors.initials: Y
authors.lastname: Yoneda
authors.forename: T
authors.initials: T
authors.lastname: Tsukihara
mesh_terms: D000595:Amino Acid Sequence; D001692:Biological Transport; D002467:Cell Nucleus / Q000378:metabolism*; D018360:Crystallography, X-Ray; D003598:Cytoskeletal Proteins / Q000737:chemistry; D028884:Karyopherins; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009038:Motion; D019913:Nuclear Localization Signals; D009687:Nuclear Proteins / Q000737:chemistry* / Q000378:metabolism*; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D018583:Pliability; D011485:Protein Binding; D017433:Protein Structure, Secondary; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D020449:Repetitive Sequences, Amino Acid; D016415:Sequence Alignment; D015534:Trans-Activators; D051176:beta Catenin
chemical_list: D003598:Cytoskeletal Proteins; D028884:Karyopherins; D019913:Nuclear Localization Signals; D009687:Nuclear Proteins; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D015534:Trans-Activators; D051176:beta Catenin