Phosducin (Pdc), a highly conserved phosphoprotein, plays an important role in the regulation of G-protein signalling, transcriptional control, and modulation of blood pressure. Pdc is negatively regulated by phosphorylation followed by binding to the 14-3-3 protein.
Our data show that the phosphorylation of the N-terminal domain of Pdc at Ser-54 and Ser-73 affects the structure of the whole Pdc molecule. Complex formation with 14-3-3 reduces the flexibility of both the N- and C-terminal domains of phosphorylated Pdc, as determined by time-resolved tryptophan and dansyl fluorescence. Therefore, our data suggest that phosphorylated Pdc undergoes a conformational change when binding to 14-3-3. These changes involve the Gtbg binding surface within the N-terminal domain of Pdc, and thus could explain the inhibitory effect of 14-3-3 on Pdc function.
|Ribbon representation of the Pdc:Gtbg complex structure (Rezabkova et al., 2012).||SAXS low-resolution structure of the 14-3-3:pRGS3 complex (Rezabkova et al., 2011).