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4wrq
From Proteopedia
(Difference between revisions)
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| - | ''' | + | ==Crystal Structure of 14-3-3 zeta with Chibby peptide== |
| + | <StructureSection load='4wrq' size='340' side='right' caption='[[4wrq]], [[Resolution|resolution]] 2.41Å' 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> | ||
| + | </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='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> | ||
| + | </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> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == 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<ref>PMID:25909186</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | + | == References == | |
| - | [[Category: | + | <references/> |
| - | [[Category: Killoran, R | + | __TOC__ |
| - | [[Category: | + | </StructureSection> |
| - | [[Category: | + | [[Category: Choy, W Y]] |
| + | [[Category: Killoran, R C]] | ||
| + | [[Category: Shilton, B H]] | ||
| + | [[Category: Hub]] | ||
| + | [[Category: Phosphorylation]] | ||
| + | [[Category: Wnt signalling]] | ||
Revision as of 12:49, 6 May 2015
Crystal Structure of 14-3-3 zeta with Chibby peptide
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