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6sad

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Revision as of 11:29, 26 August 2020

Structure of 14-3-3 gamma in complex with double phosphorylated caspase-2 peptide on Ser139 and Ser164

Structural highlights

6sad is a 3 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
NonStd Res:
Gene:	YWHAG (HUMAN)
Activity:	Caspase-2, with EC number 3.4.22.55
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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.^[1] [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^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Jin Y, Dai MS, Lu SZ, Xu Y, Luo Z, Zhao Y, Lu H. 14-3-3gamma binds to MDMX that is phosphorylated by UV-activated Chk1, resulting in p53 activation. EMBO J. 2006 Mar 22;25(6):1207-18. Epub 2006 Mar 2. PMID:16511572 doi:10.1038/sj.emboj.7601010
↑ 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

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6sad"

@@ Line 3: / Line 3: @@
 <StructureSection load='6sad' size='340' side='right'caption='[[6sad]], [[Resolution|resolution]] 2.75&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6sad]] is a 3 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=6SAD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6SAD FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6sad]] is a 3 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=6SAD OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6SAD 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>
 <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='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://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6sad FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6sad OCA], [http://pdbe.org/6sad PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6sad RCSB], [http://www.ebi.ac.uk/pdbsum/6sad PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6sad ProSAT]</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=6sad FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6sad OCA], [http://pdbe.org/6sad PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6sad RCSB], [http://www.ebi.ac.uk/pdbsum/6sad PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6sad ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 20: / Line 20: @@
 </div>
 <div class="pdbe-citations 6sad" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[14-3-3 protein 3D structures|14-3-3 protein 3D structures]]
 == References ==
 <references/>

6sad

From Proteopedia

Revision as of 11:29, 26 August 2020

Structure of 14-3-3 gamma in complex with double phosphorylated caspase-2 peptide on Ser139 and Ser164

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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