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| | <StructureSection load='6s9k' size='340' side='right'caption='[[6s9k]], [[Resolution|resolution]] 1.60Å' scene=''> | | <StructureSection load='6s9k' size='340' side='right'caption='[[6s9k]], [[Resolution|resolution]] 1.60Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6s9k]] is a 2 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=6S9K OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6S9K FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6s9k]] 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=6S9K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6S9K FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CFH:1,1,1,3,3,3-HEXAFLUOROPROPAN-2-OL'>CFH</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]] 1.6Å</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> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CFH:1,1,1,3,3,3-HEXAFLUOROPROPAN-2-OL'>CFH</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6s9k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6s9k OCA], [https://pdbe.org/6s9k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6s9k RCSB], [https://www.ebi.ac.uk/pdbsum/6s9k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6s9k ProSAT]</span></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'>[http://proteopedia.org/fgij/fg.htm?mol=6s9k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6s9k OCA], [http://pdbe.org/6s9k PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6s9k RCSB], [http://www.ebi.ac.uk/pdbsum/6s9k PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6s9k ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == 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> [[http://www.uniprot.org/uniprot/CASP2_HUMAN CASP2_HUMAN]] Involved in the activation cascade of caspases responsible for apoptosis execution. Might function by either activating some proteins required for cell death or inactivating proteins necessary for cell survival. | + | [https://www.uniprot.org/uniprot/CASP2_HUMAN CASP2_HUMAN] Involved in the activation cascade of caspases responsible for apoptosis execution. Might function by either activating some proteins required for cell death or inactivating proteins necessary for cell survival. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Caspase-2]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]]
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| | [[Category: Large Structures]] | | [[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]]
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| - | [[Category: Nl]]
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| - | [[Category: Phosphorylation]]
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| - | [[Category: Signaling protein]]
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| Structural highlights
Function
CASP2_HUMAN Involved in the activation cascade of caspases responsible for apoptosis execution. Might function by either activating some proteins required for cell death or inactivating proteins necessary for cell survival.
Publication Abstract from PubMed
Among all species, caspase-2 (C2) is the most evolutionarily conserved caspase required for effective initiation of apoptosis following death stimuli. C2 is activated through dimerization and autoproteolytic cleavage and inhibited through phosphorylation at Ser(139) and Ser(164) , within the linker between the caspase recruitment and p19 domains of the zymogen, followed by association with the adaptor protein 14-3-3, which maintains C2 in its immature form procaspase (proC2). However, the mechanism of 14-3-3-dependent inhibition of C2 activation remains unclear. Here, we report the structural characterization of the complex between proC2 and 14-3-3 by hydrogen/deuterium mass spectrometry (HDX-MS) and protein crystallography to determine the molecular basis for 14-3-3-mediated inhibition of C2 activation. Our data reveal that the 14-3-3 dimer interacts with proC2 not only through ligand-binding grooves but also through other regions outside the central channel, thus explaining the isoform-dependent specificity of 14-3-3 protein binding to proC2 and the substantially higher binding affinity of 14-3-3 protein to proC2 than to the doubly phosphorylated peptide. The formation of the complex between 14-3-3 protein and proC2 does not induce any large conformational change in proC2. Furthermore, 14-3-3 protein interacts with and masks both the nuclear localization sequence (NLS) and the C-terminal region of the p12 domain of proC2 through transient interactions in which both the p19 and p12 domains of proC2 are not firmly docked onto the surface of 14-3-3. This masked region of p12 domain is involved in caspase-2 dimerization. Therefore, 14-3-3 protein likely inhibits proC2 activation by blocking its dimerization surface.
14-3-3 protein binding blocks the dimerization interface of caspase-2.,Kalabova D, Filandr F, Alblova M, Petrvalska O, Horvath M, Man P, Obsil T, Obsilova V FEBS J. 2020 Jan 21. doi: 10.1111/febs.15215. PMID:31961068[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Kalabova D, Filandr F, Alblova M, Petrvalska O, Horvath M, Man P, Obsil T, Obsilova V. 14-3-3 protein binding blocks the dimerization interface of caspase-2. FEBS J. 2020 Jan 21. doi: 10.1111/febs.15215. PMID:31961068 doi:http://dx.doi.org/10.1111/febs.15215
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