Effect of different charges on the conformation of phosphorylated Ser-Pro motif with 2D-NMR

摘要

Proline is unique among the 20 amino acids due to its cyclic structure, which provides a backbone switch in polypeptide. Therefore the proline is very important for the structure and function of protein and peptide. Studying the folding process of denatured proteins, it has been found that several kinetic phases can be distinguished in this process, and the cis-trans isomerization of X-Pro bonds turned out to be the rate-limiting slow phase of protein renaturation, which can determine if the proteins can exert the right biological function. The conformation of the proline motif was affected by many factors, among which the most important is the phosphorylation modification. Protein phosphorylation and dephosphorylation on serine and threonine side chain is one of the most common posttranslational modifications. The reversible phosphorylation of proteins on serine/threonine residues preceding proline (Ser/Thr-Pro) is suggested to be a major regulatory mechanism for the control of a series of cell cycle events. Although phosphorylation is thought to regulate protein function by inducing conformational changes, little is known about most of these conformational changes and their significance. On the other hand, the local pH value will change the charges of phosphonate group of the phosphoproteins, which also affect the conformation of the proline motif. Hence, in this paper a series of nonphosphorylated and phosphorylated tetrapeptides including Ser-Pro motif, the most important phosphorylational modification site, have been synthesized, and the conformations of the model peptides have been studied with 2D-NMR.