tetano
Editor, Senior Moderator
Sci Rep. 2015 Oct 12;5:15055. doi: 10.1038/srep15055.
[h=1]Structure of importin-α bound to a non-classical nuclear localization signal of the influenza A virus nucleoprotein.[/h] Nakada R[SUP]1[/SUP], Hirano H[SUP]1[/SUP], Matsuura Y[SUP]1,[/SUP][SUP]2[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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 ? 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.
PMID: 26456934 [PubMed - in process]
[h=1]Structure of importin-α bound to a non-classical nuclear localization signal of the influenza A virus nucleoprotein.[/h] Nakada R[SUP]1[/SUP], Hirano H[SUP]1[/SUP], Matsuura Y[SUP]1,[/SUP][SUP]2[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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 ? 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.
PMID: 26456934 [PubMed - in process]