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| | ==Importin and NuMA complex== | | ==Importin and NuMA complex== |
| - | <StructureSection load='5gxw' size='340' side='right' caption='[[5gxw]], [[Resolution|resolution]] 2.39Å' scene=''> | + | <StructureSection load='5gxw' size='340' side='right'caption='[[5gxw]], [[Resolution|resolution]] 2.39Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5gxw]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [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=5GXW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5GXW FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5gxw]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] 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=5GXW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5GXW FirstGlance]. <br> |
| - | </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]), NUMA1, NMP22, NUMA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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]] 2.394Å</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=5gxw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5gxw OCA], [http://pdbe.org/5gxw PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5gxw RCSB], [http://www.ebi.ac.uk/pdbsum/5gxw PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5gxw 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=5gxw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5gxw OCA], [https://pdbe.org/5gxw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5gxw RCSB], [https://www.ebi.ac.uk/pdbsum/5gxw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5gxw ProSAT]</span></td></tr> |
| | </table> | | </table> |
| - | == Disease == | |
| - | [[http://www.uniprot.org/uniprot/NUMA1_HUMAN NUMA1_HUMAN]] Acute promyelocytic leukemia. | |
| | == 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/NUMA1_HUMAN NUMA1_HUMAN]] Highly abundant component of the nuclear matrix where it may serve a non-mitotic structural role, occupies the majority if the nuclear volume. Required for maintenance and establishment of the mitotic spindle poles, functionning as a tether linking bulk microtubules of the spindle to centrosomes. May be involved in coordination of the alignment of the mitotic spindle to the cellular polarity axis, which is a prerequisite for asymmetric cell divisions.<ref>PMID:19255246</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 5gxw" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 5gxw" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Importin 3D structures|Importin 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Large Structures]] |
| - | [[Category: Chang, C C]] | + | [[Category: Mus musculus]] |
| - | [[Category: Hsia, K C]] | + | [[Category: Chang C-C]] |
| - | [[Category: Huang, T L]] | + | [[Category: Hsia K-C]] |
| - | [[Category: Importin numa complex]]
| + | [[Category: Huang T-L]] |
| - | [[Category: Protein binding]]
| + | |
| 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
Ran-guanosine triphosphatase orchestrates mitotic spindle assembly by modulation of the interaction between Importin-alpha/-beta and spindle assembly factors (SAFs). The inhibition of SAFs performed by importins needs to be done without much sequestration from abundant nuclear localization signal (NLS) -containing proteins. However, the molecular mechanisms that determine NLS-binding selectivity and that inhibit activity of Importin-beta-regulated SAFs (e.g., nuclear mitotic apparatus protein [NuMA]) remain undefined. Here, we present a crystal structure of the Importin-alpha-NuMA C terminus complex showing a novel binding pattern that accounts for selective NLS recognition. We demonstrate that, in the presence of Importin-alpha, Importin-beta inhibits the microtubule-binding function of NuMA. Further, we have identified a high-affinity microtubule-binding region that lies carboxyl-terminal to the NLS, which is sterically masked by Importin-beta on being bound by Importin-alpha. Our study provides mechanistic evidence of how Importin-alpha/-beta regulates the NuMA functioning required for assembly of higher-order microtubule structures, further illuminating how Ran-governed transport factors regulate diverse SAFs and accommodate various cell demands.
Regulation of mitotic spindle assembly factor NuMA by Importin-beta.,Chang CC, Huang TL, Shimamoto Y, Tsai SY, Hsia KC J Cell Biol. 2017 Sep 22. pii: jcb.201705168. doi: 10.1083/jcb.201705168. PMID:28939615[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Chang CC, Huang TL, Shimamoto Y, Tsai SY, Hsia KC. Regulation of mitotic spindle assembly factor NuMA by Importin-beta. J Cell Biol. 2017 Sep 22. pii: jcb.201705168. doi: 10.1083/jcb.201705168. PMID:28939615 doi:http://dx.doi.org/10.1083/jcb.201705168
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