View source for 5v5p


==Structure of NLS2R of influenza A virus nucleoprotein bound to importin alpha==
<StructureSection load='5v5p' size='340' side='right'caption='[[5v5p]], [[Resolution|resolution]] 2.15&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5v5p]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Influenza_A_virus_(A/swine/Bakum/5/95(H1N1)) Influenza A virus (A/swine/Bakum/5/95(H1N1))] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5V5P OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5V5P FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.15&#8491;</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5v5p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5v5p OCA], [https://pdbe.org/5v5p PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5v5p RCSB], [https://www.ebi.ac.uk/pdbsum/5v5p PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5v5p ProSAT]</span></td></tr>
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== Function ==
[https://www.uniprot.org/uniprot/IMA1_MOUSE 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.
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== Publication Abstract from PubMed ==
The influenza A virus nucleoprotein (NP) is an essential multifunctional protein that encapsidates the viral genome and functions as an adapter between the virus and the host cell machinery. NPs from all strains of influenza A viruses contain two nuclear localization signals (NLSs): a well-studied monopartite NLS1 and a less-characterized NLS2, thought to be bipartite. Through site-directed mutagenesis and functional analysis, we found that NLS2 is also monopartite and is indispensable for viral infection. Atomic structures of importin alpha bound to two variants of NLS2 revealed NLS2 primarily binds the major-NLS binding site of importin alpha, unlike NLS1 that associates with the minor NLS-pocket. Though peptides corresponding to NLS1 and NLS2 bind weakly to importin alpha, the two NLSs synergize in the context of the full length NP to confer high avidity for importin alpha7, explaining why the virus efficiently replicates in the respiratory tract that exhibits high levels of this isoform. This study, the first to functionally characterize NLS2, demonstrates NLS2 plays an important and unexpected role in influenza A virus infection. We propose NLS1 and NLS2 form a bipartite NLS in trans, which ensures high avidity for importin alpha7 while preventing non-specific binding to viral RNA.

Synergy of two low-affinity NLSs determines the high avidity of influenza A virus nucleoprotein NP for human importin alpha isoforms.,Wu W, Sankhala RS, Florio TJ, Zhou L, Nguyen NLT, Lokareddy RK, Cingolani G, Pante N Sci Rep. 2017 Sep 12;7(1):11381. doi: 10.1038/s41598-017-11018-1. PMID:28900157<ref>PMID:28900157</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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==See Also==
*[[Importin 3D structures|Importin 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Cingolani G]]
[[Category: Lokareddy RK]]
[[Category: Sankhala RS]]