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| | ==Structure of importin a5 bound to the N-terminus of Nup50== | | ==Structure of importin a5 bound to the N-terminus of Nup50== |
| - | <StructureSection load='3tj3' size='340' side='right' caption='[[3tj3]], [[Resolution|resolution]] 2.70Å' scene=''> | + | <StructureSection load='3tj3' size='340' side='right'caption='[[3tj3]], [[Resolution|resolution]] 2.70Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3tj3]] is a 4 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=3TJ3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3TJ3 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3tj3]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TJ3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3TJ3 FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2c1t|2c1t]], [[2jdq|2jdq]]</td></tr> | + | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2c1t|2c1t]], [[2jdq|2jdq]]</div></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">KPNA1, RCH2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), NUP50, NPAP60L, PRO1146 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">KPNA1, RCH2 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), NUP50, NPAP60L, PRO1146 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=3tj3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tj3 OCA], [http://pdbe.org/3tj3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3tj3 RCSB], [http://www.ebi.ac.uk/pdbsum/3tj3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3tj3 ProSAT]</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=3tj3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tj3 OCA], [https://pdbe.org/3tj3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3tj3 RCSB], [https://www.ebi.ac.uk/pdbsum/3tj3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3tj3 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/IMA1_HUMAN IMA1_HUMAN]] 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/NUP50_HUMAN NUP50_HUMAN]] Component of the nuclear pore complex that has a direct role in nuclear protein import. Actively displaces NLSs from importin-alpha, and facilitates disassembly of the importin-alpha:beta-cargo complex and importin recycling. Interacts with multiple transport receptor proteins including CDKN1B. This interaction is required for correct intracellular transport and degradation of CDKN1B.<ref>PMID:20016008</ref> | + | [[https://www.uniprot.org/uniprot/IMA1_HUMAN IMA1_HUMAN]] 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/NUP50_HUMAN NUP50_HUMAN]] Component of the nuclear pore complex that has a direct role in nuclear protein import. Actively displaces NLSs from importin-alpha, and facilitates disassembly of the importin-alpha:beta-cargo complex and importin recycling. Interacts with multiple transport receptor proteins including CDKN1B. This interaction is required for correct intracellular transport and degradation of CDKN1B.<ref>PMID:20016008</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | ==See Also== | | ==See Also== |
| - | *[[Importin|Importin]] | + | *[[Importin 3D structures|Importin 3D structures]] |
| - | *[[Nucleoporin|Nucleoporin]] | + | *[[Nucleoporin 3D structures|Nucleoporin 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Human]] | | [[Category: Human]] |
| | + | [[Category: Large Structures]] |
| | [[Category: Cingolani, G]] | | [[Category: Cingolani, G]] |
| | [[Category: Hart, D J]] | | [[Category: Hart, D J]] |
| Structural highlights
Function
[IMA1_HUMAN] 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. [NUP50_HUMAN] Component of the nuclear pore complex that has a direct role in nuclear protein import. Actively displaces NLSs from importin-alpha, and facilitates disassembly of the importin-alpha:beta-cargo complex and importin recycling. Interacts with multiple transport receptor proteins including CDKN1B. This interaction is required for correct intracellular transport and degradation of CDKN1B.[1]
Publication Abstract from PubMed
The human genome encodes six isoforms of importin alpha that show greater than 60% sequence similarity and remarkable substrate specificity. The isoform importin alpha5 can bind phosphorylated cargos such as STAT1 and Epstein-Barr Virus Nuclear Antigen 1, as well as the influenza virus polymerase subunit PB2. In this work, we have studied the interaction of the nucleoporin Nup50 with importin alpha5. We show that the first 47 residues of Nup50 bind to the C terminus of importin alpha5 like a "clip," stabilizing the closed conformation of ARM 10. In vitro, Nup50 binds with high affinity either to empty importin alpha5 or to a preassembled complex of importin alpha5 bound to the C-terminal domain of the import cargo PB2, resulting in a trimeric complex. By contrast, PB2 can only bind with high affinity to importin alpha5 in the absence of Nup50. This suggests that Nup50 primary function may not be to actively displace the import cargo from importin alpha5 but rather to prevent cargo rebinding in preparation for recycling. This is the first evidence for a nucleoporin modulating the import reaction by directly altering the three-dimensional structure of an import adaptor.
Nucleoporin Nup50 stabilizes closed conformation of armadillo repeat 10 in importin alpha5.,Pumroy RA, Nardozzi JD, Hart DJ, Root MJ, Cingolani G J Biol Chem. 2012 Jan 13;287(3):2022-31. doi: 10.1074/jbc.M111.315838. Epub 2011 , Nov 30. PMID:22130666[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Ogawa Y, Miyamoto Y, Asally M, Oka M, Yasuda Y, Yoneda Y. Two isoforms of Npap60 (Nup50) differentially regulate nuclear protein import. Mol Biol Cell. 2010 Feb 15;21(4):630-8. doi: 10.1091/mbc.E09-05-0374. Epub 2009, Dec 16. PMID:20016008 doi:http://dx.doi.org/10.1091/mbc.E09-05-0374
- ↑ Pumroy RA, Nardozzi JD, Hart DJ, Root MJ, Cingolani G. Nucleoporin Nup50 stabilizes closed conformation of armadillo repeat 10 in importin alpha5. J Biol Chem. 2012 Jan 13;287(3):2022-31. doi: 10.1074/jbc.M111.315838. Epub 2011 , Nov 30. PMID:22130666 doi:http://dx.doi.org/10.1074/jbc.M111.315838
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