Importin α nuclear localization signal binding sites for STAT1, STAT2, and influenza a virus nucleoprotein

Item Type:	Article
Title:	Importin α nuclear localization signal binding sites for STAT1, STAT2, and influenza a virus nucleoprotein
Creators Name:	Melen, K. and Fagerlund, R. and Franke, J. and Koehler, M. and Kinnunen, L. and Julkunen, I.
Abstract:	Proteins actively transported into the nucleus via the classical nuclear import pathway contain nuclear localization signals (NLSs), which are recognized by the family of importin α molecules. Importin {alpha} contains 10 armadillo (arm) repeats, of which the N-terminal arm repeats 2–4 have been considered as the “major” NLS binding site. Interferon-activated, dimerized signal transducers and activators of transcription (STAT1 and STAT2) directly bind to importin {alpha}5 via a dimeric nonclassical NLS. Here we show by site-directed mutagenesis that the very C-terminal arm repeats 8 and 9 of importin {alpha}5 form a unique binding site for STAT1 homodimers and STAT1-STAT2 heterodimers. Influenza A virus nucleoprotein also contains a nonclassical NLS that is recognized by the C-terminal NLS binding site of importin {alpha}5, comprising arm repeats 7–9. Binding of influenza A virus nucleoprotein to importin {alpha}3 also occurs via the C-terminal arm repeats. Simian virus 40 large T antigen instead binds to the major N-terminal arm repeats of importin {alpha}3, indicating that one importin {alpha} molecule is able to use either its N- or C-terminal arm repeats for binding various NLS containing proteins.
Keywords:	{alpha} Karyopherins, Amino Acid Sequence, Amino Acid Sequence Homology, Baculoviridae, Binding Sites, Cell Line, DNA-Binding Proteins, Dimerization, Interferons, Karyopherins, Molecular Models, Molecular Sequence Data, Nuclear Localization Signals, Nucleoproteins, Phylogeny, Plasmids, Polyacrylamide Gel Electrophoresis, Polyomavirus Transforming Antigens, Protein Binding, Protein Isoforms, RNA-Binding Proteins, Site-Directed Mutagenesis, STAT1 Transcription Factor, STAT2 Transcription Factor, Tertiary Protein Structure, Trans-Activators, Viral Core Proteins, Western Blotting, Animals, Insects
Source:	Journal of Biological Chemistry
ISSN:	0021-9258
Publisher:	American Society for Biochemistry and Molecular Biology
Volume:	278
Number:	30
Page Range:	28193-28200
Date:	25 July 2003
Official Publication:	https://doi.org/10.1074/jbc.M303571200
PubMed:	View item in PubMed

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