View source for 8dp5


==Structure of the PEAK3/14-3-3 complex==
<StructureSection load='8dp5' size='340' side='right'caption='[[8dp5]], [[Resolution|resolution]] 3.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8dp5]] is a 6 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=8DP5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8DP5 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.1&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></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=8dp5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8dp5 OCA], [https://pdbe.org/8dp5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8dp5 RCSB], [https://www.ebi.ac.uk/pdbsum/8dp5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8dp5 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/PEAK3_HUMAN PEAK3_HUMAN] Probable catalytically inactive kinase (Probable). Interacts with CRK-II and antagonizes CRK-II-signaling. Prevents the formation of CRK-II-dependent membrane ruffling and lamellipodia-like extensions (PubMed:31311869).<ref>PMID:31311869</ref> <ref>PMID:31311869</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
PEAK pseudokinases are molecular scaffolds which dimerize to regulate cell migration, morphology, and proliferation, as well as cancer progression. The mechanistic role dimerization plays in PEAK scaffolding remains unclear, as there are no structures of PEAKs in complex with their interactors. Here, we report the cryo-EM structure of dimeric PEAK3 in complex with an endogenous 14-3-3 heterodimer. Our structure reveals an asymmetric binding mode between PEAK3 and 14-3-3 stabilized by one pseudokinase domain and the SHED domain of the PEAK3 dimer. The binding interface contains a canonical phosphosite-dependent primary interaction and a unique secondary interaction not observed in previous structures of 14-3-3/client complexes. Additionally, we show that PKD regulates PEAK3/14-3-3 binding, which when prevented leads to PEAK3 nuclear enrichment and distinct protein-protein interactions. Altogether, our data demonstrate that PEAK3 dimerization forms an unusual secondary interface for 14-3-3 binding, facilitating 14-3-3 regulation of PEAK3 localization and interactome diversity.

Structural insights into regulation of the PEAK3 pseudokinase scaffold by 14-3-3.,Torosyan H, Paul MD, Forget A, Lo M, Diwanji D, Pawlowski K, Krogan NJ, Jura N, Verba KA Nat Commun. 2023 Jun 19;14(1):3543. doi: 10.1038/s41467-023-38864-0. PMID:37336883<ref>PMID:37336883</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8dp5" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Jura N]]
[[Category: Paul M]]
[[Category: Torosyan H]]
[[Category: Verba KA]]