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==Crystal structure of human importin a3 bound to RCC1==
<StructureSection load='5tbk' size='340' side='right'caption='[[5tbk]], [[Resolution|resolution]] 3.45&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5tbk]] is a 16 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=5TBK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5TBK FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.45&#8491;</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=5tbk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5tbk OCA], [https://pdbe.org/5tbk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5tbk RCSB], [https://www.ebi.ac.uk/pdbsum/5tbk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5tbk ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/IMA3_HUMAN IMA3_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. In vitro, mediates the nuclear import of human cytomegalovirus UL84 by recognizing a non-classical NLS. In vitro, mediates the nuclear import of human cytomegalovirus UL84 by recognizing a non-classical NLS.
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== Publication Abstract from PubMed ==
Active nuclear import of Ran exchange factor RCC1 is mediated by importin alpha3. This pathway is essential to generate a gradient of RanGTP on chromatin that directs nucleocytoplasmic transport, mitotic spindle assembly and nuclear envelope formation. Here we identify the mechanisms of importin alpha3 selectivity for RCC1. We find this isoform binds RCC1 with one order of magnitude higher affinity than the generic importin alpha1, although the two isoforms share an identical NLS-binding groove. Importin alpha3 uses its greater conformational flexibility to wedge the RCC1 beta-propeller flanking the NLS against its lateral surface, preventing steric clashes with its Armadillo-core. Removing the beta-propeller, or inserting a linker between NLS and beta-propeller, disrupts specificity for importin alpha3, demonstrating the structural context rather than NLS sequence determines selectivity for isoform 3. We propose importin alpha3 evolved to recognize topologically complex NLSs that lie next to bulky domains or are masked by quaternary structures.Importin alpha3 facilitates the nuclear transport of the Ran guanine nucleotide exchange factor RCC1. Here the authors reveal the molecular basis for the selectivity of RCC1 for importin alpha3 vs the generic importin alpha1 and discuss the evolution of importin alpha isoforms.

Three-dimensional context rather than NLS amino acid sequence determines importin alpha subtype specificity for RCC1.,Sankhala RS, Lokareddy RK, Begum S, Pumroy RA, Gillilan RE, Cingolani G Nat Commun. 2017 Oct 17;8(1):979. doi: 10.1038/s41467-017-01057-7. PMID:29042532<ref>PMID:29042532</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 5tbk" style="background-color:#fffaf0;"></div>

==See Also==
*[[Importin 3D structures|Importin 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Cingolani G]]
[[Category: Lokareddy RK]]
[[Category: Pumroy RA]]
[[Category: Sankhala RS]]