title: A 41 amino acid motif in importin-alpha confers binding to importin-beta and hence transit into the nucleus.
abstract: The complex of importin-alpha and -beta is essential for nuclear protein import. It binds the import substrate in the cytosol, and the resulting trimeric complex moves through the nuclear pores, probably as a single entity. Importin-alpha provides the nuclear localization signal binding site, importin-beta the site of initial docking to the pore. Here we show that the conserved, basic N-terminus of importin-alpha is sufficient for importin-beta binding and essential for protein import. The fusion product of this 41 amino acid domain to a heterologous protein if transported into the nucleus in the same way as full-length importin-alpha itself. Transport is dependent on importin-beta but competed by importin-alpha. As no additional part of importin-alpha is needed for translocation, the movement which drives the import substrate complex into the nucleus appears to be generated between importin-beta and structures of the nuclear pore. The domain that binds to importin-beta appears to confer import only, but not re-export out of the nucleus, suggesting that the return of importin-alpha into the cytoplasm is not a simple reversal of its entry.
authors.affiliation: Wellcome/CRC Institute, Cambridge, UK
authors.forename: D
authors.initials: D
authors.lastname: Görlich
authors.forename: P
authors.initials: P
authors.lastname: Henklein
authors.forename: R A
authors.initials: RA
authors.lastname: Laskey
authors.forename: E
authors.initials: E
authors.lastname: Hartmann
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D001693:Biological Transport, Active; D002467:Cell Nucleus / Q000378:metabolism; D016384:Consensus Sequence; D003593:Cytoplasm / Q000378:metabolism; D018076:DNA, Complementary / Q000235:genetics; D019143:Evolution, Molecular; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D028884:Karyopherins; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009685:Nuclear Envelope / Q000378:metabolism; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D009865:Oocytes / Q000378:metabolism; D011485:Protein Binding; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014981:Xenopus
chemical_list: D018076:DNA, Complementary; D028884:Karyopherins; D009687:Nuclear Proteins; D011994:Recombinant Proteins