7a6r
From Proteopedia
(Difference between revisions)
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| - | ==== | + | ==Structure of 14-3-3 gamma in complex with DAPK2 peptide containing the 14-3-3 binding motif== |
| - | <StructureSection load='7a6r' size='340' side='right'caption='[[7a6r]]' scene=''> | + | <StructureSection load='7a6r' size='340' side='right'caption='[[7a6r]], [[Resolution|resolution]] 2.70Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7a6r]] is a 8 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=7A6R OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7A6R FirstGlance]. <br> |
| - | </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=7a6r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7a6r OCA], [https://pdbe.org/7a6r PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7a6r RCSB], [https://www.ebi.ac.uk/pdbsum/7a6r PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7a6r ProSAT]</span></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.7Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</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=7a6r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7a6r OCA], [https://pdbe.org/7a6r PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7a6r RCSB], [https://www.ebi.ac.uk/pdbsum/7a6r PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7a6r ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/DAPK2_HUMAN DAPK2_HUMAN] Calcium/calmodulin-dependent serine/threonine kinase involved in multiple cellular signaling pathways that trigger cell survival, apoptosis, and autophagy. Regulates both type I apoptotic and type II autophagic cell deaths signal, depending on the cellular setting. The former is caspase-dependent, while the latter is caspase-independent and is characterized by the accumulation of autophagic vesicles. Acts as a mediator of anoikis and a suppressor of beta-catenin-dependent anchorage-independent growth of malignant epithelial cells. May play a role in granulocytic maturation.<ref>PMID:10376525</ref> <ref>PMID:10629061</ref> <ref>PMID:21408167</ref> <ref>PMID:11230133</ref> <ref>PMID:11980920</ref> <ref>PMID:17347302</ref> <ref>PMID:18957423</ref> Isoform 2 is not regulated by calmodulin. It can phosphorylate MYL9. It can induce membrane blebbing and autophagic cell death.<ref>PMID:10376525</ref> <ref>PMID:10629061</ref> <ref>PMID:21408167</ref> <ref>PMID:11230133</ref> <ref>PMID:11980920</ref> <ref>PMID:17347302</ref> <ref>PMID:18957423</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Death-associated protein kinase 2 (DAPK2) is a CaM-regulated Ser/Thr protein kinase, involved in apoptosis, autophagy, granulocyte differentiation and motility regulation, whose activity is controlled by autoinhibition, autophosphorylation, dimerization and interaction with scaffolding proteins 14-3-3. However, the structural basis of 14-3-3-mediated DAPK2 regulation remains unclear. Here, we structurally and biochemically characterize the full-length human DAPK2:14-3-3 complex by combining several biophysical techniques. The results from our X-ray crystallographic analysis revealed that Thr369 phosphorylation at the DAPK2 C terminus creates a high-affinity canonical mode III 14-3-3-binding motif, further enhanced by the diterpene glycoside Fusicoccin A. Moreover, concentration-dependent DAPK2 dimerization is disrupted by Ca(2+)/CaM binding and stabilized by 14-3-3 binding in solution, thereby protecting the DAPK2 inhibitory autophosphorylation site Ser318 against dephosphorylation and preventing Ca(2+)/CaM binding. Overall, our findings provide mechanistic insights into 14-3-3-mediated DAPK2 inhibition and highlight the potential of the DAPK2:14-3-3 complex as a target for anti-inflammatory therapies. | ||
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| + | 14-3-3 proteins inactivate DAPK2 by promoting its dimerization and protecting key regulatory phosphosites.,Horvath M, Petrvalska O, Herman P, Obsilova V, Obsil T Commun Biol. 2021 Aug 19;4(1):986. doi: 10.1038/s42003-021-02518-y. PMID:34413451<ref>PMID:34413451</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7a6r" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[14-3-3 protein 3D structures|14-3-3 protein 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: | + | [[Category: Horvath M]] |
| + | [[Category: Obsil T]] | ||
| + | [[Category: Obsilova V]] | ||
Revision as of 12:04, 1 February 2024
Structure of 14-3-3 gamma in complex with DAPK2 peptide containing the 14-3-3 binding motif
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