4zdu

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

spinqualitylabelsall models 4zdu, resolution 2.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4zdu is a 2 chain structure with sequence from Influenza A virus (A/Puerto Rico/8/1934(H1N1)) and Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.3Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function IMA1_MOUSE Functions in nuclear protein import as an adapter protein for nuclear receptor KPNB1. Binds specifically and directly to substrates containing either a simple or bipartite NLS motif. Docking of the importin/substrate complex to the nuclear pore complex (NPC) is mediated by KPNB1 through binding to nucleoporin FxFG repeats and the complex is subsequently translocated through the pore by an energy requiring, Ran-dependent mechanism. At the nucleoplasmic side of the NPC, Ran binds to importin-beta and the three components separate and importin-alpha and -beta are re-exported from the nucleus to the cytoplasm where GTP hydrolysis releases Ran from importin. The directionality of nuclear import is thought to be conferred by an asymmetric distribution of the GTP- and GDP-bound forms of Ran between the cytoplasm and nucleus. Publication Abstract from PubMed 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 A resolution crystal structure of mouse importin-alpha1 in complex with NP ncNLS. The structure reveals that NP ncNLS binds specifically and exclusively to the minor NLS-binding site of importin-alpha. Structural and functional analyses identify key binding pockets on importin-alpha as potential targets for antiviral drug development. Unlike many other NLSs, NP ncNLS binds to the NLS-binding domain of importin-alpha weakly with micromolar affinity. These results suggest that a modest inhibitor with low affinity to importin-alpha could have anti-influenza activity with minimal cytotoxicity. Structure of importin-alpha bound to a non-classical nuclear localization signal of the influenza A virus nucleoprotein.,Nakada R, Hirano H, Matsuura Y Sci Rep. 2015 Oct 12;5:15055. doi: 10.1038/srep15055. PMID:26456934 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Importin 3D structures

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