6p6e
From Proteopedia
Structure of Mouse Importin alpha - PAC3 NLS peptide complex
Structural highlights
FunctionIMA1_MOUSE Functions in nuclear protein import as an adapter protein for nuclear receptor KPNB1. Binds specifically and directly to substrates containing either a simple or bipartite NLS motif. Docking of the importin/substrate complex to the nuclear pore complex (NPC) is mediated by KPNB1 through binding to nucleoporin FxFG repeats and the complex is subsequently translocated through the pore by an energy requiring, Ran-dependent mechanism. At the nucleoplasmic side of the NPC, Ran binds to importin-beta and the three components separate and importin-alpha and -beta are re-exported from the nucleus to the cytoplasm where GTP hydrolysis releases Ran from importin. The directionality of nuclear import is thought to be conferred by an asymmetric distribution of the GTP- and GDP-bound forms of Ran between the cytoplasm and nucleus. Publication Abstract from PubMedImportin-alpha (Impalpha) is an adaptor protein that binds to cargo proteins (containing Nuclear Localization Sequences - NLSs), for their translocation to the nucleus. The specificities of the Impalpha/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 Impalpha variants from the same organism or Impalpha of different organisms. Previously, we investigated nuclear transport of transcription factors with Neurospora crassa Impalpha (NcImpalpha). Herein, NIT-2 and PAC-3 transcription factors NLSs were studied in complex with Mus musculus Impalpha (MmImpalpha). Calorimetric assays demonstrated that the PAC-3 NLS peptide interacts with both Impalpha proteins with approximately the same affinity. The NIT-2 NLS sequence binds with high affinity to the Impalpha 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 MmImpalpha. These findings, together with previous results with Impalpha 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. Comparative study of the interactions between fungal transcription factor nuclear localization sequences with mammalian and fungal importin-alpha.,Bernardes NE, Fukuda CA, da Silva TD, de Oliveira HC, de Barros AC, Dreyer TR, Bertolini MC, Fontes MRM Sci Rep. 2020 Jan 29;10(1):1458. doi: 10.1038/s41598-020-58316-9. PMID:31996719[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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