Structure of importin-beta bound to the IBB domain of importin-alpha

Nature. 1999 May 20;399(6733):221-9. doi: 10.1038/20367.


Cytosolic proteins bearing a classical nuclear localization signal enter the nucleus bound to a heterodimer of importin-alpha and importin-beta (also called karyopherin-alpha and -beta). The formation of this heterodimer involves the importin-beta-binding (IBB) domain of importin-alpha, a highly basic amino-terminal region of roughly 40 amino-acid residues. Here we report the crystal structure of human importin-beta bound to the IBB domain of importin-alpha, determined at 2.5 A and 2.3 A resolution in two crystal forms. Importin-beta consists of 19 tandemly repeated HEAT motifs and wraps intimately around the IBB domain. The association involves two separate regions of importin-beta, recognizing structurally distinct parts of the IBB domain: an amino-terminal extended moiety and a carboxy-terminal helix. The structure indicates that significant conformational changes occur when importin-beta binds or releases the IBB domain domain and suggests how dissociation of the importin-alpha/beta heterodimer may be achieved upon nuclear entry.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Crystallography, X-Ray
  • Escherichia coli
  • Evolution, Molecular
  • Humans
  • Karyopherins
  • Models, Molecular
  • Molecular Sequence Data
  • Nuclear Proteins / chemistry*
  • Nuclear Proteins / metabolism
  • Protein Binding
  • Protein Conformation
  • Protein Structure, Secondary
  • Recombinant Proteins / chemistry
  • Repetitive Sequences, Amino Acid
  • ran GTP-Binding Protein


  • Karyopherins
  • Nuclear Proteins
  • Recombinant Proteins
  • ran GTP-Binding Protein

Associated data

  • PDB/1QGK
  • PDB/1QGR