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Reference: www.mshri.on.ca/pawson/research1.html

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14-3-3 Domains



Structure

Crystal structures of the mammalian t and x isoforms of the 14-3-3 module show that each module is composed of nine anti-parallel a helices.  Dimerization results in the formation of a negatively charged channel between the two monomers.  This channel is lined with invariant residues that mediate interactions with a phosphoserine peptide target sequence.  The figure shows the 14-3-3 x dimer complexed with phosphoserine peptide containing the 14-3-3 binding motif.

 

Domain binding and function


14-3-3 proteins are 30 kDa polypeptides with nine closely related members in mammals.  They are also found in plants and fungi.  They are involved in regulating various pathways including signal transduction, apoptosis and passage through the cell cycle. 14-3-3 proteins form homo- and hetero-dimeric cup-like structures that bind to discrete phosphoserine-containing motifs. In some instances, 14-3-3 proteins appear to export their binding partners from the nucleus to the cytoplasm in a phosphorylation- and Crm1-dependent manner.

 

Binding examples

14-3-3 Protein

Binding partner 

Function 
Cdc25 tyrosine phosphatase Cell cycle regulation
BAD (Bcl-XL binding partner) Regulation of apotosis
c-Raf Ser/Thr Kinase Regulation of kinase activity; Signal transduction
PKC Ser/Thr Kinase Signal transduction
MEKK1,2,3 Ser/Thr Kinase Signal transduction