Coupling structural disorder to biomineralization: How ions and phosphorylation control protein function

Speaker: Assistant Professor Magdalena Wojtas, Wroclaw University of Science and Technology, Poland
Series: Materials Chemistry Research Interest Group

Otoliths serve as elegant models for biologically controlled biomineralization, utilizing similar macromolecular machinery to achieve distinct polymorph selection. Here, we demonstrate how the intrinsically disordered protein Starmaker (Stm) utilizes conformational flexibility and post-translational modification to direct calcium carbonate phase selection. Stm adopts an expanded conformation with high Ca2+ capacity, and its compaction is finely tuned by monovalent ions. In the presence of Ca2+ and Mg2+, Stm undergoes liquid–liquid phase separation (LLPS), generating a fluid amorphous precursor that yields aragonite over calcite. Beyond ionic modulation, we show that native phosphorylation patterns act as an essential molecular switch for polymorph selection: Stm isolated from vaterite otoliths directs vaterite formation in vitro, whereas identical protein sequences with artificial phosphorylation or dephosphorylation yield calcite. These findings provide the first direct demonstration that a single isolated protein switches calcium carbonate polymorphs based on its phosphorylation pattern, revealing how ionic cooperative tuning and post-translational modifications govern non-classical biomineralization pathways.