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| | ==Crystal structure of mouse importin-alpha1 bound to non-phosphorylated NLS of EBNA1== | | ==Crystal structure of mouse importin-alpha1 bound to non-phosphorylated NLS of EBNA1== |
| - | <StructureSection load='5wun' size='340' side='right' caption='[[5wun]], [[Resolution|resolution]] 2.20Å' scene=''> | + | <StructureSection load='5wun' size='340' side='right'caption='[[5wun]], [[Resolution|resolution]] 2.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5wun]] 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=5WUN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5WUN FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5wun]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Human_herpesvirus_4_strain_B95-8 Human herpesvirus 4 strain B95-8] 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=5WUN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5WUN FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5wum|5wum]]</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]] 2.2Å</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=5wun FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wun OCA], [https://pdbe.org/5wun PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5wun RCSB], [https://www.ebi.ac.uk/pdbsum/5wun PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5wun 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=5wun FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wun OCA], [http://pdbe.org/5wun PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5wun RCSB], [http://www.ebi.ac.uk/pdbsum/5wun PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5wun 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. [[http://www.uniprot.org/uniprot/EBNA1_EBVB9 EBNA1_EBVB9]] Plays an essential role in replication and partitioning of viral genomic DNA during latent viral infection. During this phase, the circular double-stranded viral DNA undergoes replication once per cell cycle and is efficiently partitioned to the daughter cells. EBNA1 activates the initiation of viral DNA replication through binding to specific sites in the viral latent origin of replication, oriP. Additionally, it governs the segregation of viral episomes by mediating their attachment to host cell metaphase chromosomes. Also activates the transcription of several viral latency genes. Finally, it can counteract the stabilization of host p53/TP53 by host USP7, thereby decreasing apoptosis and increasing host cell survival.<ref>PMID:15808506</ref> | + | [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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| | </div> | | </div> |
| | <div class="pdbe-citations 5wun" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 5wun" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Importin 3D structures|Importin 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Human herpesvirus 4 strain B95-8]] |
| - | [[Category: Hirano, H]] | + | [[Category: Large Structures]] |
| - | [[Category: Matsuura, Y]] | + | [[Category: Mus musculus]] |
| - | [[Category: Nakada, R]] | + | [[Category: Hirano H]] |
| - | [[Category: Importin]] | + | [[Category: Matsuura Y]] |
| - | [[Category: Nuclear import]] | + | [[Category: Nakada R]] |
| - | [[Category: Nuclear localization signal]]
| + | |
| - | [[Category: Protein transport-peptide complex]]
| + | |
| 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
Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA1) is expressed in every EBV-positive tumor and is essential for the maintenance, replication, and transcription of the EBV genome in the nucleus of host cells. EBNA1 is a serine phosphoprotein, and it has been shown that phosphorylation of S385 in the nuclear localization signal (NLS) of EBNA1 increases the binding affinity to the nuclear import adaptor importin-alpha1 as well as importin-alpha5, and stimulates nuclear import of EBNA1. To gain insights into how phosphorylation of the EBNA1 NLS regulates nuclear import, we have determined the crystal structures of two peptide complexes of importin-alpha1: one with S385-phosphorylated EBNA1 NLS peptide, determined at 2.0 A resolution, and one with non-phosphorylated EBNA1 NLS peptide, determined at 2.2 A resolution. The structures show that EBNA1 NLS binds to the major and minor NLS-binding sites of importin-alpha1, and indicate that the binding affinity of the EBNA1 NLS to the minor NLS-binding site could be enhanced by phosphorylation of S385 through electrostatic interaction between the phosphate group of phospho-S385 and K392 of importin-alpha1 (corresponding to R395 of importin-alpha5) on armadillo repeat 8.
Structural basis for the regulation of nuclear import of Epstein-Barr virus nuclear antigen 1 (EBNA1) by phosphorylation of the nuclear localization signal.,Nakada R, Hirano H, Matsuura Y Biochem Biophys Res Commun. 2017 Feb 26;484(1):113-117. doi:, 10.1016/j.bbrc.2017.01.063. Epub 2017 Jan 17. PMID:28104399[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Nakada R, Hirano H, Matsuura Y. Structural basis for the regulation of nuclear import of Epstein-Barr virus nuclear antigen 1 (EBNA1) by phosphorylation of the nuclear localization signal. Biochem Biophys Res Commun. 2017 Feb 26;484(1):113-117. doi:, 10.1016/j.bbrc.2017.01.063. Epub 2017 Jan 17. PMID:28104399 doi:http://dx.doi.org/10.1016/j.bbrc.2017.01.063
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