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| | ==Crystal structure of Snail1 and importin beta complex== | | ==Crystal structure of Snail1 and importin beta complex== |
| - | <StructureSection load='3w5k' size='340' side='right' caption='[[3w5k]], [[Resolution|resolution]] 2.60Å' scene=''> | + | <StructureSection load='3w5k' size='340' side='right'caption='[[3w5k]], [[Resolution|resolution]] 2.60Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3w5k]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3W5K OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3W5K FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3w5k]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3W5K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3W5K FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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]] 2.6Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">KPNB1, NTF97 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), SNAI1, SNAH ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=3w5k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3w5k OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3w5k RCSB], [http://www.ebi.ac.uk/pdbsum/3w5k PDBsum]</span></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=3w5k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3w5k OCA], [https://pdbe.org/3w5k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3w5k RCSB], [https://www.ebi.ac.uk/pdbsum/3w5k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3w5k ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/IMB1_HUMAN IMB1_HUMAN]] Functions in nuclear protein import, either in association with an adapter protein, like an importin-alpha subunit, which binds to nuclear localization signals (NLS) in cargo substrates, or by acting as autonomous nuclear transport receptor. Acting autonomously, serves itself as NLS receptor. 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. Mediates autonomously the nuclear import of ribosomal proteins RPL23A, RPS7 and RPL5. Binds to a beta-like import receptor binding (BIB) domain of RPL23A. In association with IPO7 mediates the nuclear import of H1 histone. In vitro, mediates nuclear import of H2A, H2B, H3 and H4 histones. In case of HIV-1 infection, binds and mediates the nuclear import of HIV-1 Rev. Imports PRKCI into the nucleus.<ref>PMID:9687515</ref> <ref>PMID:10228156</ref> <ref>PMID:11891849</ref> [[http://www.uniprot.org/uniprot/SNAI1_HUMAN SNAI1_HUMAN]] Involved in induction of the epithelial to mesenchymal transition (EMT), formation and maintenance of embryonic mesoderm, growth arrest, survival and cell migration. Binds to 3 E-boxes of the E-cadherin/CDH1 gene promoter and to the promoters of CLDN7 and KRT8 and, in association with histone demethylase KDM1A which it recruits to the promoters, causes a decrease in dimethylated H3K4 levels and represses transcription. Associates with EGR1 and SP1 to mediate tetradecanoyl phorbol acetate (TPA)-induced up-regulation of CDKN2B, possibly by binding to the CDKN2B promoter region 5'-TCACA-3. In addition, may also activate the CDKN2B promoter by itself.<ref>PMID:10655587</ref> <ref>PMID:16096638</ref> <ref>PMID:15647282</ref> <ref>PMID:20121949</ref> <ref>PMID:20562920</ref> <ref>PMID:21952048</ref> | + | [https://www.uniprot.org/uniprot/IMB1_HUMAN IMB1_HUMAN] Functions in nuclear protein import, either in association with an adapter protein, like an importin-alpha subunit, which binds to nuclear localization signals (NLS) in cargo substrates, or by acting as autonomous nuclear transport receptor. Acting autonomously, serves itself as NLS receptor. 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. Mediates autonomously the nuclear import of ribosomal proteins RPL23A, RPS7 and RPL5. Binds to a beta-like import receptor binding (BIB) domain of RPL23A. In association with IPO7 mediates the nuclear import of H1 histone. In vitro, mediates nuclear import of H2A, H2B, H3 and H4 histones. In case of HIV-1 infection, binds and mediates the nuclear import of HIV-1 Rev. Imports PRKCI into the nucleus.<ref>PMID:9687515</ref> <ref>PMID:10228156</ref> <ref>PMID:11891849</ref> |
| - | <div style="background-color:#fffaf0;">
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| - | == Publication Abstract from PubMed ==
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| - | Snail contributes to the epithelial-mesenchymal transition by suppressing E-cadherin in transcription processes. The Snail C2H2-type zinc-finger (ZF) domain functions both as a nuclear localization signal which binds to importin beta directly and as a DNA-binding domain. Here, a 2.5 A resolution structure of four ZF domains of Snail1 complexed with importin beta is presented. The X-ray structure reveals that the four ZFs of Snail1 are required for tight binding to importin beta in the nuclear import of Snail1. The shape of the ZFs in the X-ray structure is reminiscent of a round snail, where ZF1 represents the head, ZF2-ZF4 the shell, showing a novel interaction mode, and the five C-terminal residues the tail. Although there are many kinds of C2H2-type ZFs which have the same fold as Snail, nuclear import by direct recognition of importin beta is observed in a limited number of C2H2-type ZF proteins such as Snail, Wt1, KLF1 and KLF8, which have the common feature of terminating in ZF domains with a short tail of amino acids.
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| - | Structural basis for the selective nuclear import of the C2H2 zinc-finger protein Snail by importin beta.,Choi S, Yamashita E, Yasuhara N, Song J, Son SY, Won YH, Hong HR, Shin YS, Sekimoto T, Park IY, Yoneda Y, Lee SJ Acta Crystallogr D Biol Crystallogr. 2014 Apr 1;70(Pt 4):1050-60. doi:, 10.1107/S1399004714000972. Epub 2014 Mar 19. PMID:24699649<ref>PMID:24699649</ref>
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| - | </div>
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| | ==See Also== | | ==See Also== |
| - | *[[Importin|Importin]] | + | *[[Importin 3D structures|Importin 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Choi, S]] | + | [[Category: Large Structures]] |
| - | [[Category: Lee, S J]] | + | [[Category: Choi S]] |
| - | [[Category: Park, I Y]] | + | [[Category: Lee SJ]] |
| - | [[Category: Sekimoto, T]] | + | [[Category: Park IY]] |
| - | [[Category: Shin, Y S]] | + | [[Category: Sekimoto T]] |
| - | [[Category: Son, S Y]] | + | [[Category: Shin YS]] |
| - | [[Category: Song, J]] | + | [[Category: Son SY]] |
| - | [[Category: Won, Y H]] | + | [[Category: Song J]] |
| - | [[Category: Yamashita, E]] | + | [[Category: Won YH]] |
| - | [[Category: Yasuhara, N]] | + | [[Category: Yamashita E]] |
| - | [[Category: Yoneda, Y]] | + | [[Category: Yasuhara N]] |
| - | [[Category: Importin beta]]
| + | [[Category: Yoneda Y]] |
| - | [[Category: Nuclear protein-metal binding protein complex]]
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| - | [[Category: Nuclear transport factor snail1]]
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| - | [[Category: Transcription repressor]]
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