Department for Molecular Structural Biology

Nucleo cytoplasmic trafficking

b. Importin-ß superfamily

The majority of nuclear transport receptors belong to the Importin-ß superfamily or ß-karyopherins, named after the first receptor identified. To specify the direction of transport karyopherins have been separated in importins and exportins. All members of the Importin-ß superfamily share a common structural feature, termed HEAT repeats, first identified in (Huntingtin, elongation factor 3 (EF3), protein phosphatase 2A (PP2A), and the yeast PI3-kinase TOR1(Target of Rapamycin 1). A HEAT repeat consists of two antiparalel alpha-helices separated by a short loop (Fig.2A.). The N-terminal helix is denoted A-helix and is generally located at the outside of the protein, wheras the second helix, the B-helix is directed to the inner surface of the protein. The stacking arrangement of multiple HEAT repeats leads to a superhelical overall structure as shown for importin-ß, which is composed of 19 HEAT-repeats (Fig.2B.).

Fig. 2. Structural arrangement of the Importin-ß superfamily.
(A) HEAT-repeat structure. (B) Overall Arrangement of HEAT repeats in Importin-ß.

This superhelical arrangement allows for a high dergree of flexibility, enabling the interaction with a wide range of divergent proteins (Fig.3). The shape of the superhelix depicted in green is caused upon binding to an N-terminal alpha helical structure or a protein binding along the C-terminal B-helices within Importin-ß along the central axis. The C-terminal core domain of the bound protein is most likely located on the top of Importin-ß. In the other form of Importin-ß depicted in purple, the cargo is bound to the B-helices in the central region with the main body of the bound molecule presumably lying on the left. The two conformations of Importin-ß differ in respect to overall hight and diameter.


Fig.3. Flexibility of Importin-ß.
The mode of interaction with the cargo causes different conformations of Importin-ß, which show differences in length and diameter.

Besides a high degree of structural similarity, all members of the Importin-ß superfamily share the following binding properties:

  • Ran binding by the N-terminal region (CRIme-domain)
  • NPC interaction
  • Cargo interaction

  • Further Reading

  • Biological significance of the importin-ß family-dependent nucleocytoplasmic transport pathways. Kimura M, Imamoto N. Traffic. 2014 Apr 25. doi: 10.1111/tra.12174. [Abstract]
  • Nuclear import by karyopherin-ßs: recognition and inhibition. Chook YM, Süel KE. Biochim Biophys Acta. 2011 Sep;1813(9):1593-606. doi:10.1016/j.bbamcr.2010.10.014. [Abstract]