4ZDU

Crystal structure of importin-alpha bound to a non-classical nuclear localization signal of the influenza A virus nucleoprotein

Summary for 4ZDU

• Entry DOI: 10.2210/pdb4zdu/pdb
• Descriptor: Importin subunit alpha-1, Peptide from Nucleoprotein (3 entities in total)
• Functional Keywords: importin, nls, protein transport-signaling protein complex, protein transport/signaling protein
• Biological source: Mus musculus (Mouse); More
• Total number of polymer chains: 2
• Total formula weight: 48136.02

Authors

Nakada, R.,Hirano, H.,Matsuura, Y. (deposition date: 2015-04-19, release date: 2015-10-21, Last modification date: 2023-11-08)

Primary citation

Nakada, R.,Hirano, H.,Matsuura, Y.
Structure of importin-alpha bound to a non-classical nuclear localization signal of the influenza A virus nucleoprotein
Sci Rep, 5:15055-15055, 2015

PubMed 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.

PubMed: 26456934
DOI: 10.1038/srep15055

Experimental method

X-RAY DIFFRACTION (2.3 Å)