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==Crystal structure of importin-alpha3 bound to the 53BP1 nuclear localization signal==
<StructureSection load='8hkw' size='340' side='right'caption='[[8hkw]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8hkw]] is a 4 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=8HKW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8HKW 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]] 1.9&#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=8hkw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8hkw OCA], [https://pdbe.org/8hkw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8hkw RCSB], [https://www.ebi.ac.uk/pdbsum/8hkw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8hkw ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/TP53B_HUMAN TP53B_HUMAN] Note=A chromosomal aberration involving TP53BP1 is found in a form of myeloproliferative disorder chronic with eosinophilia. Translocation t(5;15)(q33;q22) with PDGFRB creating a TP53BP1-PDGFRB fusion protein.
== Function ==
[https://www.uniprot.org/uniprot/TP53B_HUMAN TP53B_HUMAN] Plays a key role in the response to DNA damage. May have a role in checkpoint signaling during mitosis. Enhances TP53-mediated transcriptional activation.<ref>PMID:12364621</ref> <ref>PMID:17190600</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
53BP1 (TP53-binding protein 1), a key player in DNA double-strand break repair, has a classical bipartite nuclear localization signal (NLS) of sequence 1666-GKRKLITSEEERSPAKRGRKS-1686 that binds to importin-alpha, a nuclear import adaptor protein. Nucleoporin Nup153 is involved in nuclear import of 53BP1, and the binding of Nup153 to importin-alpha has been proposed to promote efficient import of classical NLS-containing proteins. Here, the ARM-repeat domain of human importin-alpha3 bound to 53BP1 NLS was crystallized in the presence of a synthetic peptide corresponding to the extreme C-terminus of Nup153 (sequence: 1459-GTSFSGRKIKTAVRRRK-1475). The crystal belonged to space group I2, with unit-cell parameters a = 95.70, b = 79.60, c = 117.44 A, beta = 95.57 degrees . The crystal diffracted X-rays to 1.9 A resolution, and the structure was solved by molecular replacement. The asymmetric unit contained two molecules of importin-alpha3 and two molecules of 53BP1 NLS. Although no convincing density was observed for the Nup153 peptide, the electron density corresponding to 53BP1 NLS was unambiguous and continuous along the entire length of the bipartite NLS. The structure revealed a novel dimer of importin-alpha3, in which two protomers of importin-alpha3 are bridged by the bipartite NLS of 53BP1. In this structure, the upstream basic cluster of the NLS is bound to the minor NLS-binding site of one protomer of importin-alpha3, whereas the downstream basic cluster of the same chain of NLS is bound to the major NLS-binding site of another protomer of importin-alpha3. This quaternary structure is distinctly different from the previously determined crystal structure of mouse importin-alpha1 bound to the 53BP1 NLS. The atomic coordinates and structure factors have been deposited in the Protein Data Bank (accession code 8HKW).

Crystallographic data of an importin-alpha3 dimer in which the two protomers are bridged by a bipartite nuclear localization signal.,Matsuura Y Data Brief. 2023 Feb 16;47:108988. doi: 10.1016/j.dib.2023.108988. eCollection , 2023 Apr. PMID:36875212<ref>PMID:36875212</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8hkw" 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: Matsuura Y]]