Intrinsically Disordered Osteopontin Fragment Orders During Interfacial Calcium Oxalate Mineralization.

Abstract

Calcium oxalate (CaC2O4) is the major component of kidney stone. The acidic osteopontin (OPN) protein in human urine can effectively inhibit the growth of CaC2O4 crystals, thereby acting as a potent stone preventer. Previous studies in bulk solution all attest to the importance of binding and recognition of OPN at the CaC2O4 mineral surface, yet molecular level insights into the active interface during CaC2O4 mineralization are still lacking. Here, we probe the structure of the central OPN fragment and its interaction with Ca2+ and CaC2O4 at the water–air interface using surface‐specific non‐linear vibrational spectroscopy. While OPN peptides remain largely disordered in solution, our results reveal that the bidentate binding of Ca2+ ions refold the interfacial peptides into well‐ordered and assembled β‐turn motifs. One critical intermediate directs mineralization by releasing structural freedom of backbone and binding side chains. These insights into the mineral interface are crucial for understanding the pathological development of kidney stones and possibly relevant for calcium oxalate biomineralization in general.