Reference - Detail
RRC ID | 35739 |
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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* Nucleocapsid Proteins 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 | 3.998 |
Times Cited | 22 |
WOS Category | BIOCHEMISTRY & MOLECULAR BIOLOGY |
Resource | |
DNA material | pGEX-NP-ncNLS (RDB13757) |