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Structure of importin-? bound to a non-classical nuclear localization signal of the influenza A virus nucleoprotein.

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-?1 in complex with NP ncNLS. The structure reveals that NP ncNLS binds specifically and exclusively to the minor NLS-binding site of importin-?. Structural and functional analyses identify key binding pockets on importin-? as potential targets for antiviral drug development. Unlike many other NLSs, NP ncNLS binds to the NLS-binding domain of importin-? weakly with micromolar affinity. These results suggest that a modest inhibitor with low affinity to importin-? could have anti-influenza activity with minimal cytotoxicity.

SUBMITTER: Nakada R

PROVIDER: S-EPMC4601014 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Structure of importin-α bound to a non-classical nuclear localization signal of the influenza A virus nucleoprotein.

Nakada Ryohei R Hirano Hidemi H Matsuura Yoshiyuki Y

Scientific reports 20151012

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- ...[more]

PMID: 26456934

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