The β-Methyne of Ile3 in the Propeptide Region of Prouroguanylin is Crucial for Chaperone Function in the Folding of the Mature Peptide, Uroguanylin

Abstract

A number of peptide hormones are expressed in vivo in the form of prepropeptides, which are subsequently processed into the biologically active mature peptides. However, the aspects of the specific role of the propeptide region remain obscure. We previously reported that uroguanylin, an endogenous ligand of guanylyl cyclase C [1], is folded into the native conformation via assistance by its propeptide region, which plays the role of an intra-molecular chaperone [2]. Our recent studies showed that the N-terminal region of prouroguanylin is important in the folding of the mature peptide, uroguanylin [3]. To further investigate the sites which are essential for the chaperone function in the N-terminal region of prouroguanylin, mutant proteins, in which the N-terminal amino acid residues were individually replaced by Gly or Ala residues (Figure 1), were prepared and their folding was examined.