Conformational Heterogeneity of Karyopherinβ2 Is Segmental

SummaryKaryopherinβ2 (Kapβ2) or transportin imports numerous RNA binding proteins into the nucleus. Kapβ2 binds substrates in the cytoplasm and targets them through the nuclear pore complex, where RanGTP dissociates them in the nucleus. Here we report the 3.0 Å crystal structure of unliganded Kapβ2, which consists of a superhelix of 20 HEAT repeats. Together with previously reported structures of NLS and Ran complexes, this structure provides understanding of conformational heterogeneity that accompanies ligand binding. The Kapβ2 superhelix is divided into three major segments. Two of them (HEAT repeats 9–13 and 14–18), which constitute the substrate binding site, are rigid elements that rotate relative to each other about a flexible hinge. The third (HEAT repeats 1–8), which constitutes the Ran binding site, exhibits conformational changes throughout its length. An analogous segmental architecture is also observed in Importinβ, suggesting that it is functionally significant and may be conserved in other import karyopherins