EVOLUTIONARY SPECIALIZATION OF THE NUCLEAR TARGETING APPARATUS

The alpha-and Beta-karyopherins (Kaps), also called importins, mediate the nuclear transport of proteins. All alpha-Kaps contain a central d omain composed of eight approximately 40 amino acid, tandemly arranged , armadillo-like (Arm) repeats. The number and order of these repeats have not changed since the common origin of fungi, plants, and mammals . Phylogenetic analysis suggests that the various alpha-Kaps fall into two groups, alpha 1 and alpha 2. Whereas animals encode both types, t he yeast. genome encodes only an alpha 1-Kap. The beta-Kaps are charac terized by 14-15 tandemly arranged I-LEAT motifs, We show that the Arm repeats of alpha-Kaps and the HEAT motifs of beta-Kaps are similar, s uggesting that the alpha-Kaps and beta-Kaps (and for that matter, all Arm and HEAT repeat-containing proteins) are members of the same prote in superfamily. Phylogenetic analysis indicates that there are at leas t three major groups of beta-Kaps, consistent with their proposed carg o specificities. We present a model in which an alpha-independent beta -Kap progenitor gave rise to the alpha-dependent beta-Kaps and the alp ha-Kaps.