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| | <StructureSection load='5v5o' size='340' side='right'caption='[[5v5o]], [[Resolution|resolution]] 2.24Å' scene=''> | | <StructureSection load='5v5o' size='340' side='right'caption='[[5v5o]], [[Resolution|resolution]] 2.24Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5v5o]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5V5O OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5V5O FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5v5o]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Influenza_A_virus Influenza A virus] 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=5V5O OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5V5O FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4zdu|4zdu]], [[5v5p|5v5p]]</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.243Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Kpna2, Rch1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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=5v5o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5v5o OCA], [https://pdbe.org/5v5o PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5v5o RCSB], [https://www.ebi.ac.uk/pdbsum/5v5o PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5v5o ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5v5o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5v5o OCA], [http://pdbe.org/5v5o PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5v5o RCSB], [http://www.ebi.ac.uk/pdbsum/5v5o PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5v5o ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://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. | + | [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. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Influenza A virus]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Mus musculus]] |
| - | [[Category: Cingolani, G]] | + | [[Category: Cingolani G]] |
| - | [[Category: Lokareddy, R K]] | + | [[Category: Lokareddy RK]] |
| - | [[Category: Sankhala, R S]] | + | [[Category: Sankhala RS]] |
| - | [[Category: Nl]]
| + | |
| - | [[Category: Nuclear import]]
| + | |
| - | [[Category: Viral protein]]
| + | |
| Structural highlights
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
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Wu W, Sankhala RS, Florio TJ, Zhou L, Nguyen NLT, Lokareddy RK, Cingolani G, Pante N. Synergy of two low-affinity NLSs determines the high avidity of influenza A virus nucleoprotein NP for human importin alpha isoforms. Sci Rep. 2017 Sep 12;7(1):11381. doi: 10.1038/s41598-017-11018-1. PMID:28900157 doi:http://dx.doi.org/10.1038/s41598-017-11018-1
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