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==Structural and mechanistical studies of the nuclear import by Importin-alpha==
<StructureSection load='5h43' size='340' side='right'caption='[[5h43]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5h43]] is a 3 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=5H43 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5H43 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]] 2.3&#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=5h43 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5h43 OCA], [https://pdbe.org/5h43 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5h43 RCSB], [https://www.ebi.ac.uk/pdbsum/5h43 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5h43 ProSAT]</span></td></tr>
</table>
== Function ==
[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.
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== Publication Abstract from PubMed ==
The histone acetyltransferase MOF (males-absent-on-the-first) acetylates the histone H4, a modification important for many biological processes, including chromatin organization, transcriptional regulation, DNA replication, recombination and repair, as well as autophagy. Depletion of MOF induces serious consequences due to the reduction of histone acetylation, such as nuclear morphological defects and cancer. Despite the critical roles of MOF in the nucleus, the structural or functional mechanisms of the nucleocytoplasmic transport of MOF remain elusive. Here, we identified novel importin alpha1-specific nuclear localization signals (NLSs) in the N-terminal of human MOF. The crystal structure of MOF NLSs in complex with importin alpha1 further revealed a unique binding mode of MOF, with two independent NLSs binding to importin alpha1 major and minor sites, respectively. The second NLS of MOF displays an unexpected alpha-helical conformation in the C-terminus, with more extensive contacts with importin alpha1 not limited in the minor site. Mutations of the key residues on MOF and importin alpha1 lead to the reduction of their interaction as well as the nuclear import of MOF, revealing an essential role of NLS2 of MOF in interacting with importin alpha1 minor site. Taken together, we provide structural mechanisms underlying the nucleocytoplasmic transport of MOF, which will be of great importance in understanding the functional regulation of MOF in various biological processes.

Structural insights into the nuclear import of the histone acetyltransferase MOF by importin alpha1.,Zheng W, Wang R, Liu X, Tian S, Yao B, Chen A, Jin S, Li Y Traffic. 2017 Oct 9. doi: 10.1111/tra.12534. PMID:28991411<ref>PMID:28991411</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 5h43" style="background-color:#fffaf0;"></div>

==See Also==
*[[Importin 3D structures|Importin 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Li Y]]
[[Category: Wang R]]