Stabilization of Mineral Precursors by Intrinsically Disordered Proteins

Biogenic nucleation and crystallization occur in confined spaces with defined interfacial properties. However, the regulatory functions of organic players in the stabilization and transport of inorganic precursors such as ion clusters, liquid-condensed phases, and amorphous particles are unclear. Given the prevalence of unstructured proteins in biogenic materials, the present study investigates the effects of biomineral-associated, intrinsically disordered protein domains with simple and repetitive amino acid compositions on mineral nucleation and their capability to form distinct supramolecular assemblies. The quantitative assessment and structural evaluation of the nucleation process reveal that disordered regions confine hydrated mineral precursors within vesicles, transiently suppressing mineral precipitation. Stabilization of the amorphous mineral is attributed to protein self-association and restructuration toward β-configurations, triggered by specific bioinorganic interactions. In consequence, the conditioned macromolecules localize at phase boundaries formed upon liquid–liquid demixing of mineral precursors and stabilize the fluidic mineral precursors against crystallization. Thus, the conformational plasticity and self-association of intrinsically disordered sequences in response to crystallization environments mediates the selection of functional macromolecular subensembles dedicated to biomaterial growth.