CONFORMATIONAL EFFECTS OF SERINE PHOSPHORYLATION IN PHOSPHOLAMBAN PEPTIDES

We have employed one- and two-dimensional H-1-NMR spectroscopy to stud y the effects of serine phosphorylation on peptide conformations, usin g cardiac phospholamban as a model system. The nonphosphorylated phosp holamban 1-20 peptide has few restraints on the conformations availabl e to it in aqueous solution. Phosphorylation at Ser16 results in great er constraints being placed on the region encompassing Arg14-Thr17, pa rticularly at neutral pH when the phosphate group is in the di-anionic form. These conformational restrictions arise from specific interacti ons between the side-chain of Arg14 acid the phosphate group. While su bstitution of phosphothreonine at position 15 causes generally similar effects to phosphoserine, aspartic acid has little effect. The result s are compared with phosphorylation effects in other systems, includin g cardiac troponin I.