View source for 9hfw


==SRC-3 (NCoA-3) peptide bound to SPOP MATH domain==
<StructureSection load='9hfw' size='340' side='right'caption='[[9hfw]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9hfw]] 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=9HFW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9HFW 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]] 1.7&#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=9hfw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9hfw OCA], [https://pdbe.org/9hfw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9hfw RCSB], [https://www.ebi.ac.uk/pdbsum/9hfw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9hfw ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/D6RDG8_HUMAN D6RDG8_HUMAN] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The adaptor protein, Speckle-type BTB/POZ protein (SPOP), recruits substrates to the cullin-3-subclass of E3 ligase for selective protein ubiquitylation. The Myddosome protein, Myeloid differentiation primary response 88 (MyD88), is ubiquitylated by the SPOP-based E3 ligase to negatively regulate immune signaling, however, the sequence rules for SPOP-mediated substrate engagement and degradation are not fully understood. Here, we show that MyD88 interacts with SPOP through a long degron that contains the established SPOP-binding consensus and an N-terminal site that we name the Q-motif. Based on sequence similarity to MyD88, we show that additional substrates, including Steroid receptor coactivator-3 (SRC-3), SET domain-containing protein 2 (SETD2) and Caprin1, engage SPOP in this manner. We show that the Q-motif is a critical determinant of these interactions in mammalian cells and determine X-ray crystal structures that show the molecular basis of SPOP associations with these proteins. These studies reveal a new consensus sequence for substrate-binding to SPOP that is necessary for substrate ubiquitylation, thus expanding the sequence rules required for SPOP-mediated E3 ligase substrate recognition.

Sequence rules for a long SPOP-binding degron required for protein ubiquitylation.,Makhlouf L, Mishra M, Makhlouf H, Manfield I, Busino L, Zeqiraj E Biochem J. 2025 Mar 27:BCJ20253041. doi: 10.1042/BCJ20253041. PMID:40178506<ref>PMID:40178506</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9hfw" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Makhlouf L]]
[[Category: Zeqiraj E]]