Structure of importin-[alpha] bound to a non-classical nuclear localization signal of the influenza A virus nucleoprotein

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...

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Bibliographic Details
Published in:Scientific reports 2015-10, Vol.5, p.15055
Main Authors: Nakada, Ryohei, Hirano, Hidemi, Matsuura, Yoshiyuki
Format: Article
Language:English
Subjects:
Affinity
Binding sites
Crystal structure
Cytotoxicity
Drug development
Influenza
Influenza A
Localization
Nuclear transport
Structure-function relationships
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Summary: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.
ISSN:2045-2322
DOI:10.1038/srep15055