View source for 7kpk


==Crystal structure of the SPOP MATH domain in complex with a fragment of Pdx1==
<StructureSection load='7kpk' size='340' side='right'caption='[[7kpk]], [[Resolution|resolution]] 1.71&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7kpk]] is a 2 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=7KPK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7KPK 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]] 1.71&#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=7kpk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7kpk OCA], [https://pdbe.org/7kpk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7kpk RCSB], [https://www.ebi.ac.uk/pdbsum/7kpk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7kpk ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/D6RDG8_HUMAN D6RDG8_HUMAN] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Speckle-type POZ protein (SPOP) is a ubiquitin ligase adaptor that binds substrate proteins and facilitates their proteasomal degradation. Most SPOP substrates present multiple SPOP-binding motifs and undergo liquid-liquid phase separation with SPOP. Pancreatic and duodenal homeobox 1 (Pdx1), an insulin transcription factor, is downregulated by interaction with SPOP. Unlike other substrates, however, Pdx1 was reported to have just one SPOP-binding (SB) motif within its C-terminal disordered region (Pdx1-C). Given this difference, we aimed to determine the specific mode of interaction of Pdx1 with SPOP and how it is similar or different to that of other SPOP substrates. Here, we identify a second SPOP-binding motif in Pdx1-C, but still find that the resulting moderate valency is insufficient to support phase separation with SPOP in cells. While Pdx1 does not phase separate with SPOP, Pdx1 and SPOP interaction prompts SPOP re-localization from nuclear speckles to the diffuse nucleoplasm. Accordingly, we find that SPOP-mediated ubiquitination activity of Pdx1 occurs in the nucleoplasm and that highly efficient Pdx1 turnover requires both SB motifs. Our results suggest that the subnuclear localization of SPOP-substrate interactions and substrate ubiquitination may be directed by the properties of the substrate itself.

Intrinsically disordered substrates dictate SPOP subnuclear localization and ubiquitination activity.,Usher ET, Sabri N, Rohac R, Boal AK, Mittag T, Showalter SA J Biol Chem. 2021 Apr 21:100693. doi: 10.1016/j.jbc.2021.100693. PMID:33894201<ref>PMID:33894201</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7kpk" style="background-color:#fffaf0;"></div>

==See Also==
*[[Speckle-type POZ protein 3D structures|Speckle-type POZ protein 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Boal AK]]
[[Category: Usher ET]]