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

Cytosolic proteins bearing a classical nuclear localization signal enter th e nucleus bound to a heterodimer of importin-alpha and importin-beta (also called karyopherin-alpha and -beta). The formation of this heterodimer invo lves the importin-beta-binding (IBB) domain of importin-alpha, a highly bas ic 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 imp ortin-alpha, determined at 2.5 Angstrom and 2.3 Angstrom resolution in two crystal forms. Importin-beta consists of 19 tandemly repeated HEAT motifs a nd wraps intimately around the IBB domain. The association involves two sep arate regions of importin-beta, recognizing structurally distinct parts of the IBB domain: an amino-terminal extended moiety and a carboxy-terminal he lix. 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 n uclear entry.