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| | ==Structure of 14-3-3 gamma in complex with caspase-2 14-3-3 binding motif Ser164== | | ==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]] 2.85Å' scene=''> | + | <StructureSection load='6gkg' size='340' side='right'caption='[[6gkg]], [[Resolution|resolution]] 2.85Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6gkg]] is a 14 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6GKG FirstGlance]. <br> | + | <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='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></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]] 2.847Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">YWHAG ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Caspase-2 Caspase-2], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.55 3.4.22.55] </span></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> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6gkg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6gkg OCA], [http://pdbe.org/6gkg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6gkg RCSB], [http://www.ebi.ac.uk/pdbsum/6gkg PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6gkg ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| - | == Function == | |
| - | [[http://www.uniprot.org/uniprot/1433G_HUMAN 1433G_HUMAN]] Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner.<ref>PMID:16511572</ref> | |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 6gkg" style="background-color:#fffaf0;"></div> | | <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 == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Caspase-2]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]] | + | [[Category: Large Structures]] |
| - | [[Category: Alblova, M]] | + | [[Category: Alblova M]] |
| - | [[Category: Obsil, T]] | + | [[Category: Obsil T]] |
| - | [[Category: Obsilova, V]] | + | [[Category: Obsilova V]] |
| - | [[Category: 14-3-3 protein]]
| + | |
| - | [[Category: Complex]]
| + | |
| - | [[Category: Phosphorylation]]
| + | |
| - | [[Category: Signaling protein]]
| + | |
| Structural highlights
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Smidova A, Alblova M, Kalabova D, Psenakova K, Rosulek M, Herman P, Obsil T, Obsilova V. 14-3-3 protein masks the nuclear localization sequence of caspase-2. FEBS J. 2018 Oct 3. doi: 10.1111/febs.14670. PMID:30281929 doi:http://dx.doi.org/10.1111/febs.14670
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