Structure of importin-β bound to the IBB domain of importin-α

Abstract

Cytosolic proteins bearing a classical nuclear localization signal enter the nucleus bound to a heterodimer of importin-α and importin-β (also called karyopherin-α and -β). The formation of this heterodimer involves the importin-β-binding (IBB) domain of importin-α, a highly basic amino-terminal region of roughly 40 amino-acid residues. Here we report the crystal structure of human importin-β bound to the IBB domain of importin-α, determined at 2.5 Å and 2.3 Å resolution in two crystal forms. Importin-β consists of 19 tandemly repeated HEAT motifs and wraps intimately around the IBB domain. The association involves two separate regions of importin-β, 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-β binds or releases the IBB domain domain and suggests how dissociation of the importin-α/β heterodimer may be achieved upon nuclear entry.