4fj3: Difference between revisions
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==14-3-3 isoform zeta in complex with a diphoyphorylated C-RAF peptide== | |||
<StructureSection load='4fj3' size='340' side='right'caption='[[4fj3]], [[Resolution|resolution]] 1.95Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4fj3]] is a 3 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=4FJ3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4FJ3 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.95Å</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=4fj3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fj3 OCA], [https://pdbe.org/4fj3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4fj3 RCSB], [https://www.ebi.ac.uk/pdbsum/4fj3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4fj3 ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
C-RAF kinase is a central component of the Ras-RAF-MEK (mitogen-activated protein kinase/extracellular signal-regulated kinase)-ERK (extracellular signal-regulated kinase) pathway, which has been shown to be activated in 30% of human tumors. 14-3-3 proteins inactivate C-RAF by binding to the two N-terminal phosphorylation-dependent binding sites surrounding S233 and S259. 14-3-3 proteins can bind two target sequences located on one polypeptide chain simultaneously, thereby increasing binding affinity compared to single-site binding and possibly allowing regulated 14-3-3 binding through gatekeeper phosphorylation. To date, it was unclear whether 14-3-3 proteins can bind the two N-terminal phosphorylation-dependent binding site of C-RAF simultaneously. Fluorescence polarization using phosphorylated peptides demonstrated that S233 is the low-affinity and S259 is the high-affinity binding site, while simultaneous engagement of both sites by 14-3-3zeta enhances affinity compared to single-site binding. Determination of a 1:1 stoichiometry for the di-phosphorylatedpeptide binding to one 14-3-3zeta dimer with isothermal titration calorimetry was supported by the crystal structure of the 14-3-3zeta/C-RAFpS233,pS259 complex. Cellular localization studies validate the significance of these sites for cytoplasmic retention of C-RAF, suggesting an extended mechanism of RAF regulation by 14-3-3 proteins. | |||
Synergistic Binding of the Phosphorylated S233- and S259-Binding Sites of C-RAF to One 14-3-3zeta Dimer.,Molzan M, Ottmann C J Mol Biol. 2012 Aug 24. PMID:22922483<ref>PMID:22922483</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4fj3" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[14-3-3 protein 3D structures|14-3-3 protein 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Molzan M]] | |||
[[Category: Ottmann C]] | |||
