Comparative study of the interactions between fungal transcription factor nuclear localization sequences with mammalian and fungal importin-alpha.

ABSTRACT: Importin-? (Imp?) is an adaptor protein that binds to cargo proteins (containing Nuclear Localization Sequences - NLSs), for their translocation to the nucleus. The specificities of the Imp?/NLS interactions have been studied, since these features could be used as important tools to find potential NLSs in nuclear proteins or even for the development of targets to inhibit nuclear import or to design peptides for drug delivery. Few structural studies have compared different Imp? variants from the same organism or Imp? of different organisms. Previously, we investigated nuclear transport of transcription factors with Neurospora crassa Imp? (NcImp?). Herein, NIT-2 and PAC-3 transcription factors NLSs were studied in complex with Mus musculus Imp? (MmImp?). Calorimetric assays demonstrated that the PAC-3 NLS peptide interacts with both Imp? proteins with approximately the same affinity. The NIT-2 NLS sequence binds with high affinity to the Imp? major binding site from both organisms, but its binding to minor binding sites reveals interesting differences due to the presence of additional interactions of NIT-2-NLS with MmImp?. These findings, together with previous results with Imp? from other organisms, indicate that the differential affinity of NLSs to minor binding sites may be also responsible for the selectivity of some cargo proteins recognition and transport.

SUBMITTER: Bernardes NE 

PROVIDER: S-EPMC6989684 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature