RRC ID 35739
Author Nakada R, Hirano H, Matsuura Y.
Title Structure of importin-α bound to a non-classical nuclear localization signal of the influenza A virus nucleoprotein.
Journal Sci Rep
Abstract A non-classical nuclear localization signal (ncNLS) of influenza A virus nucleoprotein (NP) is critical for nuclear import of viral genomic RNAs that transcribe and replicate in the nucleus of infected cells. Here we report a 2.3 Å resolution crystal structure of mouse importin-α1 in complex with NP ncNLS. The structure reveals that NP ncNLS binds specifically and exclusively to the minor NLS-binding site of importin-α. Structural and functional analyses identify key binding pockets on importin-α as potential targets for antiviral drug development. Unlike many other NLSs, NP ncNLS binds to the NLS-binding domain of importin-α weakly with micromolar affinity. These results suggest that a modest inhibitor with low affinity to importin-α could have anti-influenza activity with minimal cytotoxicity.
Volume 5
Pages 15055
Published 2015-10-12
DOI 10.1038/srep15055
PII srep15055
PMID 26456934
PMC PMC4601014
MeSH Active Transport, Cell Nucleus Animals Binding Sites Cell Nucleus / metabolism Crystallography, X-Ray Escherichia coli / genetics Escherichia coli / metabolism Gene Expression Host-Pathogen Interactions Kinetics Mice Models, Molecular Molecular Sequence Data NIH 3T3 Cells Nuclear Localization Signals* Protein Binding Protein Interaction Domains and Motifs Protein Structure, Secondary RNA-Binding Proteins / chemistry* RNA-Binding Proteins / genetics RNA-Binding Proteins / metabolism Recombinant Proteins / chemistry Recombinant Proteins / genetics Recombinant Proteins / metabolism Viral Core Proteins / chemistry* Viral Core Proteins / genetics Viral Core Proteins / metabolism alpha Karyopherins / chemistry* alpha Karyopherins / genetics alpha Karyopherins / metabolism
IF 4.011
Times Cited 22
WOS Category BIOCHEMISTRY & MOLECULAR BIOLOGY
Resource
DNA material pGEX-NP-ncNLS (RDB13757)