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

J Mol Biol. 2000 Sep 8;302(1):251-64. doi: 10.1006/jmbi.2000.4055.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Biological Transport
  • Cell Nucleus / metabolism*
  • Crystallography, X-Ray
  • Cytoskeletal Proteins / chemistry
  • Karyopherins
  • Models, Molecular
  • Molecular Sequence Data
  • Motion
  • Nuclear Localization Signals*
  • Nuclear Proteins / chemistry*
  • Nuclear Proteins / metabolism*
  • Peptide Fragments / chemistry
  • Peptide Fragments / metabolism
  • Pliability
  • Protein Binding
  • Protein Structure, Secondary
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / metabolism
  • Repetitive Sequences, Amino Acid
  • Sequence Alignment
  • Trans-Activators*
  • beta Catenin


  • Cytoskeletal Proteins
  • Karyopherins
  • Nuclear Localization Signals
  • Nuclear Proteins
  • Peptide Fragments
  • Recombinant Fusion Proteins
  • Trans-Activators
  • beta Catenin

Associated data

  • PDB/1GCJ