Crystallographic analysis of the specific yet versatile recognition of distinct nuclear localization signals by karyopherin α

摘要: Abstract Background: Karyopherin α (importin α) is an adaptor molecule that recognizes proteins containing nuclear localization signals (NLSs). The prototypical NLS able to bind karyopherin of the SV40 T antigen, and consists a short positively charged sequence motif. Distinct classes NLSs (monopartite bipartite) have been identified are only partly conserved with respect one another but nevertheless recognized by same receptor. Results: We report crystal structures two peptide complexes yeast (Kapα): human c- myc peptide, determined at 2.1 A resolution, Xenopus nucleoplasmin 2.4 resolution. Analysis these reveals determinants specificity for binding relatively hydrophobic monopartite bipartite peptide. peptides Kapα in its extended surface groove, which presents modular array tandem pockets amino acid residues. Conclusions: Monopartite different number make interactions within them. binds extensively few similar manner antigen NLS. In contrast, engages whole individually more limited overall abundant interactions, include basic clusters backbone non-conserved linker region. Versatility specific recognition relies on flexible structural framework Kapα.