Abstract
Kidney stone formation is a sophisticated pathogenic process regulated by several stone-modulatory proteins, namely inhibitors and promoters. However, the characteristics of these proteins that determine their modulatory activities have remained largely unknown. Herein, we investigated potential characteristics of inhibitors and promoters involved in the stone-forming process by comparing amino acid contents, various physico-chemical properties, and calcium- and oxalate-binding properties of all proteins identified from normal urine (NU), stone former urine (SFU), and stone matrix (SM). Simple comparisons among the three groups showed that SM proteins apparently differed from NU and SFU proteins for almost all parameters, whereas no significant differences were detected between NU and SFU proteins. We then compared the proteins that were uniquely found in NU&SM with those uniquely found in SFU&SM, as it was hypothesized that they preferentially acted as stone inhibitors and promoters, respectively. The analyses revealed that proteins rich in amino acids with negative charges, normalized van der Waals volume of 2.95-4.0 and exposed solvent accessibility, acidic proteins, high molecular weight (MW) proteins, stable proteins, and hydrophilic proteins tended to be the stone inhibitors. On the other hand, proteins rich in aromatic and polar amino acids, basic proteins, low-MW proteins, unstable proteins, and hydrophobic proteins tended to be the stone promoters. These findings may help predict the stone-modulatory activities of proteins in urine and SM, and may inform the molecular design of kidney stone therapies.