The identification and structural analysis of potential 14-3-3 interaction sites on the bone regulator protein Schnurri-3
14-3-3 proteins regulate many intracellular processes and their ability to bind in subtly different fashions to their numerous partner proteins provides attractive drug-targeting points for a range of diseases. Schnurri-3 is a suppressor of mouse bone formation and a candidate target for novel osteoporosis therapeutics, and thus it is of interest to determine whether it interacts with 14-3-3. In this work, potential 14-3-3 interaction sites on mammalian Schnurri-3 were identified by an in silico analysis of its protein sequence. Using fluorescence polarization, isothermal titration calorimetry and X-ray crystallography, it is shown that synthetic peptides containing either phosphorylated Thr869 or Ser542 can indeed interact with 14-3-3, with the latter capable of forming an interprotein disulfide bond with 14-3-3 σ : a hitherto unreported phenomenon.
Source: Acta Crystallographica Section F - Category: Biochemistry Authors: Soini, L. Leysen, S. Crabbe, T. Davis, J. Ottmann, C. Tags: bone regulator protein Schnurri-3 X-ray protein crystallography phosphorylation fluorescence polarization disulfide bonds 14-3-3 modes research communications Source Type: research