View source for 6gkg


==Structure of 14-3-3 gamma in complex with caspase-2 14-3-3 binding motif Ser164==
<StructureSection load='6gkg' size='340' side='right'caption='[[6gkg]], [[Resolution|resolution]] 2.85&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6gkg]] is a 14 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=6GKG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6GKG 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]] 2.847&#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=6gkg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6gkg OCA], [https://pdbe.org/6gkg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6gkg RCSB], [https://www.ebi.ac.uk/pdbsum/6gkg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6gkg ProSAT]</span></td></tr>
</table>
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== Publication Abstract from PubMed ==
Caspase-2 is an apical protease responsible for the proteolysis of cellular substrates directly involved in mediating apoptotic signaling cascades. Caspase-2 activation is inhibited by phosphorylation followed by binding to the scaffolding protein 14-3-3, which recognizes two phosphoserines located in the linker between the caspase recruitment domain and the p19 domains of the caspase-2 zymogen. However, the structural details of this interaction and the exact role of 14-3-3 in the regulation of caspase-2 activation remain unclear. Moreover, the caspase-2 region with both 14-3-3-binding motifs also contains the nuclear localization sequence (NLS), thus suggesting that 14-3-3 binding may regulate the subcellular localization of caspase-2. Here, we report a structural analysis of the 14-3-3zeta:caspase-2 complex using a combined approach based on small angle X-ray scattering, NMR, chemical cross-linking, and fluorescence spectroscopy. The structural model proposed in this study suggests that phosphorylated caspase-2 and 14-3-3zeta form a compact and rigid complex in which the p19 and the p12 domains of caspase-2 are positioned within the central channel of the 14-3-3 dimer and stabilized through interactions with the C-terminal helices of both 14-3-3zeta protomers. In this conformation, the surface of the p12 domain, which is involved in caspase-2 activation by dimerization, is sterically occluded by the 14-3-3 dimer, thereby likely preventing caspase-2 activation. In addition, 14-3-3 protein binding to caspase-2 masks its NLS. Therefore, our results suggest that 14-3-3 protein binding to caspase-2 may play a key role in regulating caspase-2 activation. DATABASE: The atomic coordinates and structure factors have been deposited in the Protein Data Bank, www.ww pdb.org (PDB ID codes 6GKF and 6GKG).

14-3-3 protein masks the nuclear localization sequence of caspase-2.,Smidova A, Alblova M, Kalabova D, Psenakova K, Rosulek M, Herman P, Obsil T, Obsilova V FEBS J. 2018 Oct 3. doi: 10.1111/febs.14670. PMID:30281929<ref>PMID:30281929</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 6gkg" style="background-color:#fffaf0;"></div>

==See Also==
*[[14-3-3 protein 3D structures|14-3-3 protein 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Alblova M]]
[[Category: Obsil T]]
[[Category: Obsilova V]]