PDBsum entry 4zdu

Protein transport/signaling protein

PDB id: 4zdu

Contents

Protein chains

416 a.a.

12 a.a.

Waters ×80

References listed in PDB file

Key reference

• Title: Structure of importin-α Bound to a non-Classical nuclear localization signal of the influenza a virus nucleoprotein.
• Authors: R.Nakada, H.Hirano, Y.Matsuura.
• Ref.: Sci Rep, 2015, 5, 15055. [DOI no: 10.1038/srep15055]
• PubMed id: 26456934

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.