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4wrq

From Proteopedia

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Crystal Structure of 14-3-3 zeta with Chibby peptide

Structural highlights

4wrq is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.409Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

1433Z_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] ^[2] ^[3] ^[4] ^[5]

Publication Abstract from PubMed

The partially disordered Chibby (Cby) is a conserved nuclear protein that antagonizes the Wnt/beta-catenin signaling pathway. By competing with the Tcf/Lef family proteins for binding to beta-catenin, Cby abrogates the beta-catenin-mediated transcription of Wnt signaling genes. Additionally, upon phosphorylation on S20 by the kinase Akt, Cby forms a complex with 14-3-3 to facilitate the nuclear export of beta-catenin, which represents another crucial mechanism for the regulation of Wnt signaling. To obtain a mechanistic understanding of the 14-3-3/Cby interaction, we have extensively characterized the complex using X-ray crystallography, nuclear magnetic resonance (NMR) spectroscopy, and isothermal titration calorimetry (ITC). The crystal structure of the human 14-3-3zeta/Cby protein-peptide complex reveals a canonical binding mode; however the residue at the +2 position from the phosphorylated serine is shown to be uniquely oriented relative to other solved structures of 14-3-3 complexes. Our ITC results illustrate that although the phosphorylation of S20 is essential for Cby to recognize 14-3-3, residues flanking the phosphorylation site also contribute to the binding affinity. However, as is commonly observed in other 14-3-3/phosphopeptide crystal structures, residues of Cby flanking the 14-3-3 binding motif lack observable electron density. To obtain a more detailed binding interface, we have completed the backbone NMR resonance assignment of 14-3-3zeta. NMR titration experiments reveal that residues outside of the 14-3-3 conserved binding cleft, namely a flexible loop consisting of residues 203-210, are also involved in binding Cby. By using a combined X-ray and NMR approach, we have dissected the molecular basis of the 14-3-3/Cby interaction.

Structural Analysis of the 14-3-3zeta/Chibby Interaction Involved in Wnt/beta-Catenin Signaling.,Killoran RC, Fan J, Yang D, Shilton BH, Choy WY PLoS One. 2015 Apr 24;10(4):e0123934. doi: 10.1371/journal.pone.0123934., eCollection 2015. PMID:25909186^[6]

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

References

↑ Dubois T, Rommel C, Howell S, Steinhussen U, Soneji Y, Morrice N, Moelling K, Aitken A. 14-3-3 is phosphorylated by casein kinase I on residue 233. Phosphorylation at this site in vivo regulates Raf/14-3-3 interaction. J Biol Chem. 1997 Nov 14;272(46):28882-8. PMID:9360956
↑ Zheng W, Zhang Z, Ganguly S, Weller JL, Klein DC, Cole PA. Cellular stabilization of the melatonin rhythm enzyme induced by nonhydrolyzable phosphonate incorporation. Nat Struct Biol. 2003 Dec;10(12):1054-7. Epub 2003 Oct 26. PMID:14578935 doi:10.1038/nsb1005
↑ Tsuruta F, Sunayama J, Mori Y, Hattori S, Shimizu S, Tsujimoto Y, Yoshioka K, Masuyama N, Gotoh Y. JNK promotes Bax translocation to mitochondria through phosphorylation of 14-3-3 proteins. EMBO J. 2004 Apr 21;23(8):1889-99. Epub 2004 Apr 8. PMID:15071501 doi:10.1038/sj.emboj.7600194
↑ Ganguly S, Weller JL, Ho A, Chemineau P, Malpaux B, Klein DC. Melatonin synthesis: 14-3-3-dependent activation and inhibition of arylalkylamine N-acetyltransferase mediated by phosphoserine-205. Proc Natl Acad Sci U S A. 2005 Jan 25;102(4):1222-7. Epub 2005 Jan 11. PMID:15644438 doi:0406871102
↑ Gu YM, Jin YH, Choi JK, Baek KH, Yeo CY, Lee KY. Protein kinase A phosphorylates and regulates dimerization of 14-3-3 epsilon. FEBS Lett. 2006 Jan 9;580(1):305-10. Epub 2005 Dec 19. PMID:16376338 doi:S0014-5793(05)01485-7
↑ Killoran RC, Fan J, Yang D, Shilton BH, Choy WY. Structural Analysis of the 14-3-3zeta/Chibby Interaction Involved in Wnt/beta-Catenin Signaling. PLoS One. 2015 Apr 24;10(4):e0123934. doi: 10.1371/journal.pone.0123934., eCollection 2015. PMID:25909186 doi:http://dx.doi.org/10.1371/journal.pone.0123934

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/4wrq"

Categories: Homo sapiens | Large Structures | Choy WY | Killoran RC | Shilton BH

@@ Line 1: / Line 1: @@
 ==Crystal Structure of 14-3-3 zeta with Chibby peptide==
-<StructureSection load='4wrq' size='340' side='right' caption='[[4wrq]], [[Resolution|resolution]] 2.41&Aring;' scene=''>
+<StructureSection load='4wrq' size='340' side='right'caption='[[4wrq]], [[Resolution|resolution]] 2.41&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4wrq]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4WRQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4WRQ FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4wrq]] is a 4 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=4WRQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4WRQ 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]] 2.409&#8491;</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=4wrq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4wrq OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4wrq RCSB], [http://www.ebi.ac.uk/pdbsum/4wrq PDBsum]</span></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=4wrq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4wrq OCA], [https://pdbe.org/4wrq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4wrq RCSB], [https://www.ebi.ac.uk/pdbsum/4wrq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4wrq ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/1433Z_HUMAN 1433Z_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:9360956</ref> <ref>PMID:14578935</ref> <ref>PMID:15071501</ref> <ref>PMID:15644438</ref> <ref>PMID:16376338</ref>
+[https://www.uniprot.org/uniprot/1433Z_HUMAN 1433Z_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:9360956</ref> <ref>PMID:14578935</ref> <ref>PMID:15071501</ref> <ref>PMID:15644438</ref> <ref>PMID:16376338</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 16: / Line 18: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4wrq" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[14-3-3 protein 3D structures|14-3-3 protein 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Choy, W Y]]
+[[Category: Homo sapiens]]
-[[Category: Killoran, R C]]
+[[Category: Large Structures]]
-[[Category: Shilton, B H]]
+[[Category: Choy WY]]
-[[Category: Hub]]
+[[Category: Killoran RC]]
-[[Category: Phosphorylation]]
+[[Category: Shilton BH]]
-[[Category: Wnt signalling]]

4wrq

From Proteopedia

Current revision

Crystal Structure of 14-3-3 zeta with Chibby peptide

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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