Prorenin has high affinity multiple binding sites for (pro)renin receptor.

An important role of the decoy peptide sequence has recently been suggested in vitro for the binding of prorenin to the (pro)renin receptor [PRR]. In this study, other prospective crucial regions in renin and prorenin responsible for their interaction with PRR were investigated using various kinds of peptides, e.g., the "hinge" S149QGVLKEDVF158 designed from the structure of renin also common to prorenin, L1PPTDTTTF8P, L1PPTDTTTFKRIFLKR15P and the decoy (R10PIFLKRMPSI19P) designed from the predicted structure of prorenin. For the kinetic analysis, the recombinant hPRR was immobilized on the biosensor surface through a specific anti-PRR antibody. In case of the equilibrium state analysis, the PRR was directly adsorbed on plastic wells for observing the bindings of renin/prorenin. The dissociation constants (KD) for the bindings of renin and prorenin to the pre-adsorbed receptors were 4.5 and 1.0 nM, respectively, similar to those stated in the kinetic study by BIAcore assay. The "hinge" region peptide bound to PRR in a dose-dependent manner with a KD estimated 17.0 nM which was five times higher than that of the decoy. The KD values for L1PPTDTTTF8P and L1PPTDTTTFKRIFLKR15P were 52 and 7.6 nM, respectively. The "hinge" peptide, as the decoy, inhibited the bindings of renin and prorenin to PRR. The inhibition constant (Ki) for the binding of renin and prorenin by the decoy and "hinge" were 16.7 and 15.1, and 37.1 and 30.7 nM, respectively. These in vitro studies suggest that renin has a single and prorenin has at least two high affinity binding sites for the PRR.