Figure 1

Structure of importin β. (a) Importin β is composed of 19 helical-repeat motifs (HEAT repeats). Each consists of an A and a B helix connected by a short turn, which in HEAT-8 is replaced by an acidic loop critical for the regulation of substrate binding and release. The HEAT repeats 1-8 are required for high-affinity binding to RanGTP [4,5]. The importin-β-binding (IBB) domain of importin α interacts mainly with residues located in repeats 7-19 of importin β [6]. The binding site for nucleoporins of the NPC is located between residues 152 and 352, corresponding to repeats 4-8 [4,5]. On the basis of the crystal structure, the A helices of HEAT repeats 5 and 6 and a region between HEAT repeats 6 and 7 are thought to be critical for recognition of the FxFG motif [9]. N, amino terminus; C, carboxyl terminus. (b) Structure of importin β bound to the IBB domain of importin α (adapted from [6]). Importin β (yellow) forms a superhelical structure that wraps like a snail around the IBB domain (blue). The 19 HEAT repeats share a common core of 21 residues, comprising the A helix with about three turns and the B helix with about four turns. The helices critical for the interaction with FxFG-repeat nucleoporins [9] are in green. Important residues for interaction with RanGTP [8] are in red. Note the acidic loop, which contacts both RanGTP and the IBB domain (white arrow).